Complexes

ABSTRACT

The present invention provides a palladium(II) complex of formula (1). 
     
       
         
         
             
             
         
       
     
     R 12 , m, and X are described in the specification. 
     The invention also provides a process for the preparation of the complex, and its use in carbon-carbon and carbon-heteroatom coupling reactions.

This application is a divisional of U.S. patent application Ser. No.16/686,960, filed Nov. 18, 2019, which is a divisional of U.S. patentapplication Ser. No. 16/284,841, filed Feb. 25, 2019, now U.S. Pat. No.10,858,382, which is a divisional of U.S. patent application Ser. No.15/318,106, filed Dec. 12, 2016, now U.S. Pat. No. 10,253,056, which isa US national stage of International patent Application No.PCT/GB2015/050835, filed Mar. 20, 2015, which claims priority to U.S.Provisional Patent Application No. 62/011,168, filed Jun. 12, 2014, allapplications of which are incorporated by reference herein.

The present invention relates to optionally substituted π-allylpalladium complexes and their use thereof in coupling reactions.

WO2011/161451 (to Johnson Matthey PLC) describes π-allyl complexes, suchas π-allyl palladium complexes and π-allyl nickel complexes.

Faller et al (Organometallics, 2004, 23, 2179-2185) describes thepreparation of the complex (crotyl)Pd(Cy₂P-biphenyl)Cl in mechanisticinvestigations. Faller et al neither disclose nor suggest that thecomplex may be used a precatalyst for coupling reactions.

The use of [(allyl)PdCl]₂ or [(cinnamyl)PdCl]₂ in combination withbiaryl/heteroaryl phosphine ligands, such as Buchwald ligands incoupling reactions has proven to be of limited and unpredictablesuccess. In an attempt to overcome the limitations of catalystgeneration from palladium sources such as [(allyl)PdCl]₂, Pd(dba)_(x)(x=1, 1.5 or 2), or Pd(OAc)₂ with Buchwald ligand combinations, theBuchwald group at MIT has introduced a library of three generations ofpalladacycle precatalysts utilizing bulky biarylphosphines as shownbelow.

The palladacycles, however, demonstrate a number of limitations.Firstly, the synthesis of the 1^(st) generation palladacycles requiresseveral steps including the generation of an unstable intermediate[(TMEDA)PdMe₂]. The syntheses of the 2^(nd) and 3^(rd) generationpalladacycles require the use of potentially toxic 2-aminobiphenyl,which can be contaminated with the highly toxic 4-isomer, requiring theneed for high purity raw material. Furthermore, the activation of the2^(nd) and 3^(rd) generation palladacycles generates an equivalent ofgenotoxic carbazole. The starting material aminobiphenyl and theby-product carbazole can contaminate reaction mixtures. Hence,purification can be complicated, in addition to the consideration ofhealth and safety concerns involved in handling these materials.Moreover, the reductively eliminated carbazole (as illustrated in thefollowing figure) can consume aryl-electrophile starting material andalso significantly retard the rate of some cross-coupling reactions.

The activation of the very recent N-substituted 3^(rd) generationpalladacycles generates an equivalent of either N-methylcarbazole orN-phenylcarbazole and little is known about their toxicity. TheN-substituted version of the 3^(rd) generation palladacycles alsorequire an additional synthetic step to prepare relative to theunsubstituted analogues.

There remains a need to provide palladium precatalysts with well-definedligand/palladium ratios that overcome the limitations in the prior art.

SUMMARY OF THE INVENTION

In many cases, allyl dimers such as [(allyl)PdCl]₂ do not function wellas palladium sources with biarylphosphines and there are difficulties informing active catalysts with the allyl dimer/Buchwald ligandcombination. The present inventors, however, have discovered a class ofoptionally substituted π-allylpalladium complexes, which may be employedto effect a variety of coupling reactions, such as C—N and C—C bondformation reactions. In certain embodiments, the π-allyl complexes arehighly active catalysts. In certain embodiments, the π-allyl complexesare stable to air and moisture at ambient temperatures.

In one aspect, the invention provides a palladium(II) complex of formula(1):

wherein:R₁ and R₂ are independently organic groups having 1-20 carbon atoms, orR₁ and R₂ are linked to form a ring structure with E;R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are independently —H or organicgroups having 1-20 carbon atoms; orR₁/R₃ or R₂/R₃ forms a ring structure with the atoms to which they areattached and in this instance R₄/R₅, R₅/R₆, R₇/R₈, R₈/R₉, R₉/R₁₀ orR₁₀/R₁₁ may independently form a ring structure with the carbon atoms towhich they are attached or R₁, R₂, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁are as defined above;R₁₂ is an organic group having 1-20 carbon atoms;m is 0, 1, 2, 3, 4 or 5;E is P or As; andX is a coordinating anionic ligand;

provided that the palladium complex of formula (1) is not(π-crotyl)PdCl(dicyclohexylphosphino-2-biphenyl).

In another aspect, the invention provides a palladium complex of formula(2):

wherein:R₁₈ and R₁₉ are independently selected from the group consisting of -Me,-Et, —^(n)Pr, —^(i)Pr, —^(n)Bu, —^(i)Bu, cyclohexyl and cycloheptyl;R₁₂ is an organic group having 1-20 carbon atoms;R₂₀, R₂₁, R₂₂, R₂₃ and R₂₄ are independently —H or organic groups having1-20 carbon atoms; or one or both pairs selected from R₂₀/R₂₁ or R₂₂/R₂₃may independently form a ring structure with the atoms to which they areattached;m is 0, 1, 2, 3, 4 or 5; andX is a coordinating anionic ligand.

In another aspect, the invention provides a process for the preparationof a complex of formula (1) or a complex of formula (2) comprising thestep of reacting a complex of formula (3) with a monodentate biarylligand of formula (4) or a monodentate bi-heteroaryl tertiary phosphineligand of formula (5) to form the complex of formula (1) or the complexof formula (2),

wherein,R₁ and R₂ are independently organic groups having 1-20 carbon atoms, orR₁ and R₂ are linked to form a ring structure with E;R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are independently —H or organicgroups having 1-20 carbon atoms; orone or more pairs selected from R₁/R₃, R₂/R₃, R₃/R₄, R₄/R₅, R₅/R₆,R₇/R₈, R₈/R₉, R₉/R₁₀ or R₁₀/R₁₁ independently may form a ring structurewith the carbon atoms to which they are attached;R₁₂ is an organic group having 1-20 carbon atoms;R₁₈ and R₁₉ are independently selected from the group consisting of Me,-Et, —^(n)Pr, —^(i)Pr, —^(n)Bu, —^(i)Bu, cyclohexyl and cycloheptyl;R₂₀, R₂₁, R₂₂, R₂₃ and R₂₄ are independently —H organic groups having1-20 carbon atoms; orone or both pairs selected from R₂₀/R₂₁ or R₂₂/R₂₃ independently mayform a ring structure with the atoms to which they are attached;m is 0, 1, 2, 3, 4 or 5;E is P or As; andX is a coordinating anionic ligand;provided that the palladium complex of formula (1) is not(π-crotyl)PdCl(dicyclohexylphosphino-2-biphenyl).

In another aspect, the present invention provides a process for carryingout a carbon-carbon coupling reaction in the presence of a catalyst, theprocess comprising:

(a) the use of a complex of formula (1):

wherein:R₁ and R₂ are independently organic groups having 1-20 carbon atoms, orR₁ and R₂ are linked to form a ring structure with E;R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are independently —H or organicgroups having 1-20 carbon atoms; orR₁/R₃ or R₂/R₃ forms a ring structure with the atoms to which they areattached and in this instance R₄/R₅, R₅/R₆, R₇/R₈, R₈/R₉, R₉/R₁₀ orR₁₀/R₁₁ may independently form a ring structure with the carbon atoms towhich they are attached or R₁, R₂, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁are as defined above; R₁₂ is an organic group having 1-20 carbon atoms;m is 0, 1, 2, 3, 4 or 5;E is P or As; andX is a coordinating anionic ligand;or:(b) a complex of formula (2) as defined herein.

In another aspect, the invention provides a process for carrying out acarbon-heteroatom coupling reaction in the presence of a catalyst, theprocess comprising:

(a) the use of a complex of formula (1):

wherein:R₁ and R₂ are independently organic groups having 1-20 carbon atoms, orR₁ and R₂ are linked to form a ring structure with E;R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are independently —H or organicgroups having 1-20 carbon atoms; orR₁/R₃ or R₂/R₃ forms a ring structure with the atoms to which they areattached and in this instance R₄/R₅, R₅/R₆, R₇/R₈, R₈/R₉, R₉/R₁₀ orR₁₀/R₁₁ may independently form a ring structure with the carbon atoms towhich they are attached or R₁, R₂, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁are as defined above;R₁₂ is an organic group having 1-20 carbon atoms;m is 0, 1, 2, 3, 4 or 5;E is P or As; andX is a coordinating anionic ligand;or:(b) a complex of formula (2) as defined herein.

In another aspect, the invention provides the use of a complex offormula (1) or a complex of formula (2) as a catalyst in carbon-carboncoupling reactions, wherein:

(a) the complex of formula (1) is:

wherein:R₁ and R₂ are independently organic groups having 1-20 carbon atoms, orR₁ and R₂ are linked to form a ring structure with E;R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are independently —H or organicgroups having 1-20 carbon atoms; orR₁/R₃ or R₂/R₃ forms a ring structure with the atoms to which they areattached and in this instance R₄/R₅, R₅/R₆, R₇/R₈, R₈/R₉, R₉/R₁₀ orR₁₀/R₁₁ may independently form a ring structure with the carbon atoms towhich they are attached or R₁, R₂, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁are as defined above;R₁₂ is an organic group having 1-20 carbon atoms;m is 0, 1, 2, 3, 4 or 5;E is P or As; andX is a coordinating anionic ligand;and:(b) the complex of formula (2) as defined herein.

In another aspect, the invention provides the use of a complex offormula (1) or a complex of formula (2) as a catalyst incarbon-heteroatom coupling reactions, wherein:

(a) the complex of formula (1) is:

wherein:R₁ and R₂ are independently organic groups having 1-20 carbon atoms, orR₁ and R₂ are linked to form a ring structure with E;R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are independently —H or organicgroups having 1-20 carbon atoms; orR₁/R₃ or R₂/R₃ forms a ring structure with the atoms to which they areattached and in this instance R₄/R₅, R₅/R₆, R₇/R₈, R₈/R₉, R₉/R₁₀ orR₁₀/R₁₁ may independently form a ring structure with the carbon atoms towhich they are attached or R₁, R₂, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁are as defined above; R₁₂ is an organic group having 1-20 carbon atoms;m is 0, 1, 2, 3, 4 or 5;E is P or As; andX is a coordinating anionic ligand;and:(b) the complex of formula (2) is as defined herein.

Definitions

The point of attachment of a moiety or substituent is represented by“-”. For example, —OH is attached through the oxygen atom.

“Alkyl” refers to a straight-chain or branched saturated hydrocarbongroup. In certain embodiments, the alkyl group may have from 1-20 carbonatoms, in certain embodiments from 1-15 carbon atoms, in certainembodiments, 1-8 carbon atoms. The alkyl group may be unsubstituted.Alternatively, the alkyl group may be substituted. Unless otherwisespecified, the alkyl group may be attached at any suitable carbon atomand, if substituted, may be substituted at any suitable atom. Typicalalkyl groups include but are not limited to methyl, ethyl, n-propyl,iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, n-hexyland the like.

The term “cycloalkyl” is used to denote a saturated carbocyclichydrocarbon radical. The cycloalkyl group may have a single ring ormultiple condensed rings. In certain embodiments, the cycloalkyl groupmay have from 3-15 carbon atoms, in certain embodiments, from 3-10carbon atoms, in certain embodiments, from 3-8 carbon atoms. Thecycloalkyl group may be unsubstituted. Alternatively, the cycloalkylgroup may be substituted. Unless other specified, the cycloalkyl groupmay be attached at any suitable carbon atom and, if substituted, may besubstituted at any suitable atom. Typical cycloalkyl groups include butare not limited to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl andthe like.

“Alkoxy” refers to an optionally substituted group of the formulaalkyl-O— or cycloalkyl-O—, wherein alkyl and cycloalkyl are as definedabove.

“Alkoxyalkyl” refers to an optionally substituted group of the formulaalkoxy-alkyl-, wherein alkoxy and alkyl are as defined above.

“Aryl” refers to an aromatic carbocyclic group. The aryl group may havea single ring or multiple condensed rings. In certain embodiments, thearyl group can have from 6-20 carbon atoms, in certain embodiments from6-15 carbon atoms, in certain embodiments, 6-12 carbon atoms. The arylgroup may be unsubstituted. Alternatively, the aryl group may besubstituted. Unless otherwise specified, the aryl group may be attachedat any suitable carbon atom and, if substituted, may be substituted atany suitable atom. Examples of aryl groups include, but are not limitedto, phenyl, naphthyl, anthracenyl and the like.

“Arylalkyl” refers to an optionally substituted group of the formulaaryl-alkyl-, where aryl and alkyl are as defined above.

“Coupling” refers to a chemical reaction in which two molecules or partsof a molecule join together (Oxford Dictionary of Chemistry, SixthEdition, 2008).

“Halo” or “hal” refers to —F, —Cl, —Br and —I.

“Heteroalkyl” refers to a straight-chain or branched saturatedhydrocarbon group wherein one or more carbon atoms are independentlyreplaced with one or more heteroatoms (e.g. nitrogen, oxygen, phosphorusand/or sulfur atoms). The heteroalkyl group may be unsubstituted.Alternatively, the heteroalkyl group may be substituted. Unlessotherwise specified, the heteroalkyl group may be attached at anysuitable atom and, if substituted, may be substituted at any suitableatom. Examples of heteralkyl groups include but are not limited toethers, thioethers, primary amines, secondary amines, tertiary aminesand the like.

“Heterocycloalkyl” refers to a saturated cyclic hydrocarbon groupwherein one or more carbon atoms are independently replaced with one ormore heteroatoms (e.g. nitrogen, oxygen, phosphorus and/or sulfuratoms). The heterocycloalkyl group may be unsubstituted. Alternatively,the heterocycloalkyl group may be substituted. Unless otherwisespecified, the heterocycloalkyl group may be attached at any suitableatom and, if substituted, may be substituted at any suitable atom.Examples of heterocycloalkyl groups include but are not limited toepoxide, morpholinyl, piperadinyl, piperazinyl, thirranyl, pyrrolidinyl,pyrazolidinyl, imidazolidinyl, thiazolidinyl, thiomorpholinyl and thelike.

“Heteroaryl” refers to an aromatic carbocyclic group wherein one or morecarbon atoms are independently replaced with one or more heteroatoms(e.g. nitrogen, oxygen, phosphorus and/or sulfur atoms). The heteroarylgroup may be unsubstituted. Alternatively, the heteroaryl group may besubstituted. Unless otherwise specified, the heteroaryl group may beattached at any suitable atom and, if substituted, may be substituted atany suitable atom. Examples of heteroaryl groups include but are notlimited to thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl,isothiazolyl, oxazolyl, isoxazolyl, triazolyl, thiadiazolyl, thiophenyl,oxadiazolyl, pyridinyl, pyrimidyl, benzoxazolyl, benzthiazolyl,benzimidazolyl, indolyl, quinolinyl and the like.

“Substituted” refers to a group in which one or more hydrogen atoms areeach independently replaced with substituents (e.g. 1, 2, 3, 4, 5 ormore) which may be the same or different. Examples of substituentsinclude but are not limited to -halo, —C(halo)₃, —R_(a), ═O, ═S,—O—R_(a), —S—R_(a), —NR_(a)R_(b), —CN, —NO₂, —C(O)—R_(a), —COOR_(a),—C(S)—R_(a), —C(S)OR_(a), —S(O)₂OH, —S(O)₂—R_(a), —S(O)₂NR_(a)R_(b),—O—S(O)—R_(a) and —CONR_(a)R_(b), such as -halo, —C(halo)₃ (e.g. CF₃),—R_(a), —O—R_(a), —NR_(a)R_(b), —CN, or —NO₂. R_(a) and R_(b) areindependently selected from the groups consisting of H, alkyl, aryl,arylalkyl, heteroalkyl, heteroaryl, or R_(a) and R_(b) together with theatom to which they are attached form a heterocycloalkyl group. R_(a) andR_(b) may be unsubstituted or further substituted as defined herein.

“Thioalkyl” refers to an optionally substituted group of the formulaalkyl-S— or cycloalkyl-S—, wherein alkyl and cycloalkyl are as definedabove.

DETAILED DESCRIPTION

In one aspect, the present invention provides a palladium(II) complex offormula (1):

wherein:R₁ and R₂ are independently organic groups having 1-20 carbon atoms, orR₁ and R₂ are linked to form a ring structure with E;R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are independently —H or organicgroups having 1-20 carbon atoms; orR₁/R₃ or R₂/R₃ forms a ring structure with the atoms to which they areattached and in this instance R₄/R₅, R₅/R₆, R₇/R₈, R₈/R₉, R₉/R₁₀ orR₁₀/R₁₁ may independently form a ring structure with the carbon atoms towhich they are attached or R₁, R₂, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁are as defined above; R₁₂ is an organic group having 1-20 carbon atoms;m is 0, 1, 2, 3, 4 or 5;E is P or As; andX is a coordinating anionic ligand;

provided that the palladium complex of formula (1) is not(π-crotyl)PdCl(dicyclohexylphosphino-2-biphenyl).

When E is a phosphorus atom (i.e. P), the complex of formula (1) is apalladium(II) complex comprising a monodentate biaryl tertiary phosphineligand, a coordinating anionic ligand and an optionally substitutedπ-allyl group.

When E is an arsenic atom (i.e. As), the complex of formula (1) is apalladium(II) complex comprising a monodentate biaryl tertiary arsineligand, a coordinating anionic ligand and an optionally substitutedπ-allyl group.

R₁ and R₂ may be the same or different. In one embodiment, R₁ and R₂ arethe same. In another embodiment, R₁ and R₂ are different. R₁ and R₂ areselected up to the limitations imposed by stability and the rules ofvalence. R₁ and R₂ may be independently selected from the groupconsisting of substituted and unsubstituted straight-chain alkyl,substituted and unsubstituted branched-chain alkyl, substituted andunsubstituted cycloalkyl, substituted and unsubstituted aryl, andsubstituted and unsubstituted heteroaryl wherein the heteroatoms areindependently selected from sulfur, nitrogen and oxygen. R₁ and R₂ mayindependently be substituted or unsubstituted branched- orstraight-chain alkyl groups such as methyl, ethyl, n-propyl, iso-propyl,n-butyl, iso-butyl, sec-butyl, tert-butyl, pentyl (e.g. n-pentyl orneopentyl), hexyl, heptyl, octyl, nonyl, decyl, dodecyl or stearyl,cycloalkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl or adamantly, or aryl groups such as phenyl, naphthyl oranthracyl. In one embodiment, the alkyl groups may be optionallysubstituted with one or more (e.g. 1, 2, 3, 4, or 5) substituents eachof which may be the same or different such as halide (F, Cl, Br or I) oralkoxy groups, e.g. methoxy, ethoxy or propoxy. The aryl group may beoptionally substituted with one or more (e.g. 1, 2, 3, 4, or 5)substituents each of which may be the same or different such as halide(F, Cl, Br or I), straight- or branched-chain alkyl (e.g. C₁-C₁₀),alkoxy (e.g. C₁-C₁₀ alkoxy), straight- or branched-chain (dialkyl)amino(e.g. C₁-C₁₀ dialkyl)amino), heterocycloalkyl (e.g. C₃₋₁₀heterocycloalkyl groups, such as morpholinyl and piperadinyl) ortri(halo)methyl (e.g. F₃C—). Suitable substituted aryl groups includebut are not limited to 4-dimethylaminophenyl, 4-methylphenyl,3,5-dimethylphenyl, 4-methoxyphenyl, 4-methoxy-3,5-dimethylphenyl and3,5-di(trifluoromethyl)phenyl. Substituted or unsubstituted heteroarylgroups such as pyridyl may also be used. In an alternative embodiment,R₁ and R₂ are linked to form a ring structure with E, preferably 4- to7-membered rings. Preferably, R₁ and R₂ are the same and are tert-butyl,cyclohexyl, phenyl or substituted phenyl groups, such as3,5-di(trifluoromethyl)phenyl. R₁ and R₂ may be independently selectedfrom the group consisting of -Me, -Et, —^(n)Pr, —^(i)Pr, —^(n)Bu,—^(i)Bu, cyclohexyl and cycloheptyl.

R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are independently —H or organicgroups having 1-20 carbon atoms. R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁are selected up to the limitations imposed by stability and the rules ofvalence. R₃, R₄, R₅ and R₆ may be independently selected from the groupconsisting of —H, substituted and unsubstituted straight-chain alkyl,substituted and unsubstituted branched-chain alkyl, substituted andunsubstituted cycloalkyl, substituted and unsubstituted alkoxy,substituted and unsubstituted aryl, substituted and unsubstitutedheteroaryl, substituted and unsubstituted —N(alkyl)₂ (wherein the alkylgroups may be the same or different and are independently selected fromstraight-chain or branched-chain groups), substituted and unsubstituted—N(cycloalkyl)₂ (wherein the cycloalkyl groups may be the same ordifferent), substituted and unsubstituted —N(aryl)₂ (wherein the arylgroups may be the same or different), substituted and unsubstituted—N(heteroaryl)₂ (wherein the heteroaryl groups may be the same ordifferent) and substituted and unsubstituted heterocycloalkyl groups.The heteroatoms in the heteraryl or heterocycloalkyl groups may beindependently selected from sulfur, nitrogen and/or oxygen. In oneembodiment, the alkyl groups may be optionally substituted with one ormore (e.g. 1, 2, 3, 4, or 5) substituents each of which may be the sameor different such as halide (F, Cl, Br or I), alkoxy groups, e.g.methoxy, ethoxy or propoxy. The aryl group may be optionally substitutedwith one or more (e.g. 1, 2, 3, 4, or 5) substituents each of which maybe the same or different such as halide (F, Cl, Br or I), straight- orbranched-chain alkyl (e.g. C₁-C₁₀), alkoxy (e.g. C₁-C₁₀ alkoxy),straight- or branched-chain (dialkyl)amino (e.g. (C₁-C₁₀ dialkyl)amino),heterocycloalkyl (e.g. C₃₋₁₀ heterocycloalkyl groups, such asmorpholinyl and piperadinyl) or tri(halo)methyl (e.g. F₃C—). Suitablesubstituted aryl groups include but are not limited to 2-, 3- or4-dimethylaminophenyl, 2-, 3- or 4-methylphenyl, 2,3- or3,5-dimethylphenyl, 2-, 3- or 4-methoxyphenyl and4-methoxy-3,5-dimethylphenyl. Substituted or unsubstituted heteroarylgroups such as pyridyl may also be used. Suitable unsubstituted—N(alkyl)₂ groups include but are not limited to —NMe₂, —NEt₂ and —NPr₂(n- or i-). A suitable unsubstituted —N(cycloalkyl)₂ group includes butis not limited to —N(Cy)₂. Suitable substituted —N(alkyl)₂ groupsinclude but are not limited to —N(CH₂CH₂OMe)₂ and —N(CF₃)₂. Suitableunsubstituted —N(aryl)₂ groups include but are not limited to —NPh₂.Suitable substituted —N(aryl)₂ groups include but are not limited to—N(2-, 3- or 4-dimethylaminophenyl)₂, —N(2-, 3- or 4-methylphenyl)₂,—N(2,3- or 3,5-dimethylphenyl)₂, —N(2-, 3- or 4-methoxyphenyl)₂ and—N(4-methoxy-3,5-dimethylphenyl)₂. Suitable unsubstituted—N(heteroaryl)₂ groups include but are not limited to —N(furyl)₂ and—N(pyridyl)₂. Substituted and unsubstituted heterocycloalkyl groupsinclude but are not limited to C₄₋₈-heterocycloalkyl groups, such aspiperidinyl and morpholinyl.

R₃, R₄, R₅ and R₆ may be independently selected from the groupconsisting of —H, unsubstituted straight-chain alkyl, unsubstitutedbranched-chain alkyl, unsubstituted cycloalkyl, unsubstituted alkoxy,unsubstituted —N(alkyl)₂ (wherein the alkyl groups may be the same ordifferent and may be independently selected from straight-chain orbranched-chain groups) and unsubstituted —N(aryl)₂ (wherein the arylgroups may be the same or different). Branched- or straight-chain alkylgroups may include groups such as methyl, ethyl, n-propyl, iso-propyl,n-butyl, iso-butyl, sec-butyl, tert-butyl, pentyl (e.g. n-pentyl orneopentyl), hexyl, heptyl, octyl, nonyl, decyl, dodecyl or stearyl.Cycloalkyl groups may include groups such as cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl or adamantyl. Alkoxy groups may include groupssuch as methoxy (—OMe), ethoxy (—OEt), n-propoxy (—O-n-Pr), iso-propoxy(—O-i-Pr), n-butoxy (—O-n-Bu), iso-butoxy (—O-i-Bu), sec-butoxy(—O-s-Bu), tert-butoxy (—O-t-Bu), —O-pentyl, —O-hexyl, —O-heptyl,—O-octyl, —O-nonyl, —O-decyl, —O-dodecyl. —N(alkyl)₂ groups may includegroups such as —NMe₂, —NEt₂, —N(n-Pr)₂ or —N(i-Pr)₂.

R₃, R₄, R₅ and R₆ may be independently selected from the groupconsisting of —H, unsubstituted —N(alkyl)₂ (wherein the alkyl groups maybe the same or different and may be independently selected fromstraight-chain or branched-chain groups) and unsubstituted —N(aryl)₂(wherein the aryl groups may be the same or different).

R₃, R₄, R₅ and R₆ may be independently selected from the groupconsisting of —H, unsubstituted straight-chain alkyl, unsubstitutedbranched-chain alkyl, unsubstituted cycloalkyl and unsubstituted alkoxy.

In one embodiment, each of R₃, R₄, R₅ and R₆ are —H.

In another embodiment, at least one of R₃, R₄, R₅ and R₆ is selectedfrom a group which is not —H. For example, one of R₃, R₄, R₅ and R₆ maybe selected from a group which is not —H, such as two of R₃, R₄, R₅ andR₆, three of R₃, R₄, R₅ and R₆ or all of R₃, R₄, R₅ and R₆.

In another embodiment, two of R₃, R₄, R₅ and R₆ are —H, and the othertwo of R₃, R₄, R₅ and R₆ are independently selected from the groupconsisting of unsubstituted straight-chain alkyl, unsubstitutedbranched-chain alkyl, unsubstituted cycloalkyl and unsubstituted alkoxy.In another embodiment, two of R₃, R₄, R₅ and R₆ are —H (e.g. R₄ and R₅),and the other two of R₃, R₄, R₅ and R₆ (e.g. R₃ and R₆) areindependently selected from the group consisting of C₁₋₅-alkyl and—O—C₁₋₅-alkyl, such as Me, -Et, —Pr (n- or i-), —Bu (n-, i- or t-),—OMe, —OEt, —OPr (n- or i-) and —OBu (n-, i- or t-), for example, Me,-Et, —OMe and -OEt.

In another embodiment, two of R₃, R₄, R₅ and R₆ are H (e.g. R₄ and R₅),and the other two of R₃, R₄, R₅ and R₆ (e.g. R₃ and R₆) are selectedfrom the group consisting of unsubstituted straight-chain alkyl,unsubstituted branched-chain alkyl, unsubstituted cycloalkyl andunsubstituted alkoxy. In a preferred embodiment, two of R₃, R₄, R₅ andR₆ are H, and the other two of R₃, R₄, R₅ and R₆ are selected from thegroup consisting of C₁₋₅-alkyl and —O—C₁₋₅-alkyl, such as Me, -Et, —Pr(n- or i-), —Bu (n-, i- or t-), —OMe, —OEt, —OPr (n- or i-) and —OBu(n-, i- or t-), for example, Me, -Et, —OMe and —OEt. In one particularlypreferred embodiment, R₄ and R₅ are H, and R₃ and R₆ are OMe.

R₇, R₈, R₉, R₁₀ and R₁₁ may be independently selected from the groupconsisting of H, substituted and unsubstituted straight-chain alkyl,substituted and unsubstituted branched-chain alkyl, substituted andunsubstituted cycloalkyl, substituted and unsubstituted alkoxy,substituted and unsubstituted aryl, substituted and unsubstitutedheteroaryl, substituted and unsubstituted —N(alkyl)₂ (wherein the alkylgroups may be the same or different and are independently selected fromstraight-chain or branched-chain groups), substituted and unsubstituted—N(cycloalkyl)₂ (wherein the cycloalkyl groups may be the same ordifferent), substituted and unsubstituted —N(aryl)₂ (wherein the arylgroups may be the same or different), substituted and unsubstituted—N(heteroaryl)₂ (wherein the heteroaryl groups may be the same ordifferent) and substituted and unsubstituted heterocycloalkyl groups.The heteroatoms in the heteroaryl or heterocycloalkyl groups may beindependently selected from sulfur, nitrogen or/and oxygen. In oneembodiment, the alkyl groups may be optionally substituted with one ormore (e.g. 1, 2, 3, 4, or 5) substituents each of which may be the sameor different such as halide (F, Cl, Br or I), alkoxy groups, e.g.methoxy, ethoxy or propoxy. The aryl group may be optionally substitutedwith one or more (e.g. 1, 2, 3, 4, or 5) substituents each of which maybe the same or different such as halide (F, Cl, Br or I), straight- orbranched-chain alkyl (e.g. C₁-C₁₀), alkoxy (e.g. C₁-C₁₀ alkoxy),straight- or branched-chain (dialkyl)amino (e.g. C₁-C₁₀ dialkyl)amino),heterocycloalkyl (e.g. C₃₋₁₀ heterocycloalkyl groups, such asmorpholinyl and piperadinyl) or tri(halo)methyl (e.g. F₃C—). Suitablesubstituted aryl groups include but are not limited to 2-, 3- or4-dimethylaminophenyl, 2-, 3- or 4-methylphenyl, 2,3- or3,5-dimethylphenyl, 2-, 3- or 4-methoxyphenyl and4-methoxy-3,5-dimethylphenyl. Substituted or unsubstituted heteroarylgroups such as pyridyl may also be used. Suitable unsubstitutedN(alkyl)₂ groups include but are not limited to —NMe₂, —NEt₂ and —NPr₂(n- or i-). A suitable unsubstituted —N(cycloalkyl)₂ group includes butis not limited to —N(Cy)₂. Suitable substituted N(alkyl)₂ groups includebut are not limited to —N(CH₂CH₂OMe)₂ and —N(CF₃)₂. Suitableunsubstituted —N(aryl)₂ groups include but are not limited to —NPh₂.Suitable substituted —N(aryl)₂ groups include but are not limited to—N(2-, 3- or 4-dimethylaminophenyl)₂, —N(2-, 3- or 4-methylphenyl)₂,—N(2,3- or 3,5-dimethylphenyl)₂, —N(2-, 3- or 4-methoxyphenyl)₂ andN(4-methoxy-3,5-dimethylphenyl)₂. Suitable unsubstituted N(heteroaryl)₂groups include but are not limited to —N(furyl)₂ and —N(pyridyl)₂.Substituted and unsubstituted heterocycloalkyl groups includeC₄₋₈-heterocycloalkyl groups, such as piperidinyl and morpholinyl. R₇,R₈, R₉, R₁₀ and R₁₁ may be independently selected from the groupconsisting of —H, unsubstituted straight-chain alkyl, unsubstitutedbranched-chain alkyl, unsubstituted cycloalkyl, unsubstituted alkoxy,unsubstituted —N(alkyl)₂ (wherein the alkyl groups may be the same ordifferent and may be independently selected from straight-chain orbranched-chain groups) and unsubstituted —N(aryl)₂ (wherein the arylgroups may be the same or different). Branched- or straight-chain alkylgroups may include groups such as methyl, ethyl, n-propyl, iso-propyl,n-butyl, iso-butyl, sec-butyl, tert-butyl, pentyl (e.g. n-pentyl orneopentyl), hexyl, heptyl, octyl, nonyl, decyl, dodecyl or stearyl.Cycloalkyl groups may include groups such as cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl or adamantyl. Alkoxy groups may include groupssuch as methoxy (—OMe), ethoxy (—OEt), n-propoxy (—O-n-Pr), iso-propoxy(—O-i-Pr), n-butoxy (—O-n-Bu), iso-butoxy (—O-i-Bu), sec-butoxy(—O-s-Bu), tert-butoxy (—O-t-Bu), —O-pentyl, —O-hexyl, —O-heptyl,—O-octyl, —O-nonyl, —O-decyl, —O-dodecyl. —N(alkyl)₂ groups may includegroups such as —NMe₂, —NEt₂, —N(n-Pr)₂ or —N(i-Pr)₂.

R₇, R₈, R₉, R₁₀ and R₁₁ may be independently selected from the groupconsisting of —H, unsubstituted —N(alkyl)₂ (wherein the alkyl groups maybe the same or different and may be independently selected fromstraight-chain or branched-chain groups) and unsubstituted —N(aryl)₂(wherein the aryl groups may be the same or different).

R₇, R₈, R₉, R₁₀ and R₁₁ may be independently selected from the groupconsisting of —H, unsubstituted straight-chain alkyl, unsubstitutedbranched-chain alkyl, unsubstituted cycloalkyl and unsubstituted alkoxy.

In another embodiment, at least one of R₇, R₈, R₉, R₁₀ and R₁₁ isselected from a group which is not H. For example, one of R₇, R₈, R₉,R₁₀ and R₁₁ may be selected from a group a group which is not —H, suchas two of R₇, R₈, R₉, R₁₀ and R₁₁ (e.g. R₇ and R₁₁), three of R₇, R₈,R₉, R₁₀ and R₁₁ (e.g. R₇, R₉ and R₁₁), four of R₇, R₈, R₉, R₁₀ and R₁₁or all of R₇, R₈, R₉, R₁₀ and R₁₁.

In one embodiment, each of R₇, R₈, R₉, R₁₀ and R₁₁ are —H.

In another embodiment, four of R₇, R₈, R₉, R₁₀ and R₁₁ are —H (e.g. R₈,R₉, R₁₀ and R₁₁), and the other one of R₇, R₈, R₉, R₁₀ and R₁₁ (e.g. R₇)is selected from the group consisting of unsubstituted straight-chainalkyl, unsubstituted branched-chain alkyl, unsubstituted cycloalkyl,unsubstituted alkoxy, unsubstituted —N(alkyl)₂ (wherein the alkyl groupsmay be the same or different and may be independently selected fromstraight-chain or branched-chain groups) and unsubstituted —N(aryl)₂(wherein the aryl groups may be the same or different).

In another embodiment, four of R₇, R₈, R₉, R₁₀ and R₁₁ are —H (e.g. R₈,R₉, R₁₀ and R₁₁), and the other one of R₇, R₈, R₉, R₁₀ and R₁₁ (e.g. R₇)is selected from the group consisting of C₁₋₅-alkyl, —O—C₁₋₅-alkyl and—N(C₁₋₅-alkyl)₂ such as -Me, -Et, —Pr (n- or i-), -Bu (n-, i- or t-),—OMe, —OEt, —OPr (n- or i-), —OBu (n-, i- or t-), —NMe₂, —NEt₂,—N(n-Pr)₂ or —N(i-Pr)₂, for example, -Me, -Et, -n-Pr, -i-Pr, —OMe, —OEt,—O-n-Pr, —O-i-Pr, —NMe₂, —NEt₂. For example, R₈, R₉, R₁₀ and R₁₁ are —H,and R₇ is selected from C₁₋₅-alkyl, —O—C₁₋₅-alkyl and —N(C₁₋₅-alkyl)₂groups, such as those described above. In another embodiment, R₈, R₉,R₁₀ and R₁₁ are —H, and R₇ is selected from the group consisting of—OMe, —O-i-Pr, —NMe₂, —NEt₂, —N(n-Pr)₂ and —N(i-Pr)₂, such as —OMe and—NMe₂.

In another embodiment, three of R₇, R₈, R₉, R₁₀ and R₁₁ are —H (e.g. R₈,R₉ and R₁₀), and the other two of R₇, R₈, R₉, R₁₀ and R₁₁ (e.g. R₇ andR₁₁) are independently selected from the group consisting ofunsubstituted straight-chain alkyl, unsubstituted branched-chain alkyl,unsubstituted cycloalkyl, unsubstituted alkoxy, unsubstituted —N(alkyl)₂(wherein the alkyl groups may be the same or different and may beindependently selected from straight-chain or branched-chain groups) andunsubstituted —N(aryl)₂ (wherein the aryl groups may be the same ordifferent).

In one embodiment, three of R₇, R₈, R₉, R₁₀ and R₁₁ are —H (e.g. R₈, R₉and R₁₀), and the other two of R₇, R₈, R₉, R₁₀ and R₁₁ (e.g. R₇ and R₁₁)are selected from the group consisting of unsubstituted straight-chainalkyl, unsubstituted branched-chain alkyl, unsubstituted cycloalkyl,unsubstituted alkoxy, unsubstituted —N(alkyl)₂ (wherein the alkyl groupsmay be the same or different and may be independently selected fromstraight-chain or branched-chain groups) and unsubstituted —N(aryl)₂(wherein the aryl groups may be the same or different).

In another embodiment, three of R₇, R₈, R₉, R₁₀ and R₁₁ are —H (e.g. R₈,R₉ and R₁₀), and the other two of R₇, R₈, R₉, R₁₀ and R₁₁ (e.g. R₇ andR₁₁) are independently selected from the group consisting of C₁₋₅-alkyl,—O—C₁₋₅-alkyl and —N(C₁₋₅-alkyl)₂ such as -Me, -Et, —Pr (n- or i-), -Bu(n-, i- or t-), —OMe, —OEt, —OPr (n- or i-), —OBu (n-, i- or t-), —NMe₂,—NEt₂, —N(n-Pr)₂ or —N(i-Pr)₂, for example, -Me, -Et, -n-Pr, -i-Pr,—OMe, —OEt, —O-n-Pr, —O-i-Pr, —NMe₂, —NEt₂. For example, R₈, R₉ and R₁₀are —H, and R₇ and R₁₁ are independently selected from C₁₋₅-alkyl,—O—C₁₋₅-alkyl and —N(C₁₋₅-alkyl)₂ groups, such as those described above.In another embodiment, R₈, R₉ and R₁₀ are —H, and R₇ and R₁₁ areindependently selected from the group consisting of —OMe, —O-i-Pr,—NMe₂, —NEt₂, —N(n-Pr)₂ and —N(i-Pr)₂, such as —OMe and —O-i-Pr.

In a preferred embodiment, three of R₇, R₈, R₉, R₁₀ and R₁₁ are —H (e.g.R₈, R₉ and R₁₀), and the other two of R₇, R₈, R₉, R₁₀ and R₁₁ (e.g. R₇and R₁₁) are selected from the group consisting of C₁₋₅-alkyl,—O—C₁₋₅-alkyl and —N(C₁₋₅-alkyl)₂ such as -Me, -Et, —Pr (n- or i-), -Bu(n-, i- or t-), —OMe, —OEt, —OPr (n- or i-), —OBu (n-, i- or t-), —NMe₂,—NEt₂, —N(n-Pr)₂ or —N(i-Pr)₂, for example, -Me, -Et, -n-Pr, -i-Pr,—OMe, —OEt, —O-n-Pr, —O-i-Pr, —NMe₂, —NEt₂. In a particularly preferredembodiment, R₈, R₉ and R₁₀ are —H, and R₇ and R₁₁ are independentlyselected from C₁₋₅-alkyl, —O—C₁₋₅-alkyl and —N(C₁₋₅-alkyl)₂ groups, suchas those described above. In an especially preferred embodiment, R₈, R₉and R₁₀ are —H, and R₇ and R₁₁ are selected from the group consisting of—OMe, —O-i-Pr, —NMe₂, —NEt₂, —N(n-Pr)₂ and —N(i-Pr)₂, such as —OMe and—O-i-Pr.

In another embodiment, two of R₇, R₈, R₉, R₁₀ and R₁₁ are —H (e.g. R₉and R₁₀), and the other three of R₇, R₈, R₉, R₁₀ and R₁₁ (e.g. R₇, R₉and R₁₁) are independently selected from the group consisting ofunsubstituted straight-chain alkyl, unsubstituted branched-chain alkyl,unsubstituted cycloalkyl, unsubstituted alkoxy, unsubstituted —N(alkyl)₂(wherein the alkyl groups may be the same or different and may beindependently selected from straight-chain or branched-chain groups) andunsubstituted —N(aryl)₂ (wherein the aryl groups may be the same ordifferent).

In another embodiment, two of R₇, R₈, R₉, R₁₀ and R₁₁ are —H (e.g. R₉and R₁₀), and the other three of R₇, R₈, R₉, R₁₀ and R₁₁ (e.g. R₇, R₉and R₁₁) are selected from the group consisting of unsubstitutedstraight-chain alkyl, unsubstituted branched-chain alkyl, unsubstitutedcycloalkyl, unsubstituted alkoxy, unsubstituted —N(alkyl)₂ (wherein thealkyl groups may be the same or different and may be independentlyselected from straight-chain or branched-chain groups) and unsubstituted—N(aryl)₂ (wherein the aryl groups may be the same or different).

In one preferred embodiment, two of R₇, R₈, R₉, R₁₀ and R₁₁ are —H (e.g.R₉ and R₁₀), and the other three of R₇, R₈, R₉, R₁₀ and R₁₁ (e.g. R₇, R₉and R₁₁) are independently selected from the group consisting ofC₁₋₅-alkyl, —O—C₁₋₅-alkyl and —N(C₁₋₅-alkyl)₂, such as -Me, -Et, —Pr (n-or i-), -Bu (n-, i- or t), —OMe, —OEt, —OPr (n- or i-), —OBu (n-, i- ort-), —NMe₂, —NEt₂, —N(n-Pr)₂ or —N(i-Pr)₂, for example, -Me, -Et, -n-Pr,-i-Pr, —OMe, —OEt, —O-n-Pr, —O-i-Pr, —NMe₂, —NEt₂. In a particularlypreferred embodiment, R₈ and R₁₀ are —H, and R₇, R₉ and R₁₁ areindependently selected from —C₁₋₅-alkyl groups, such as those describedabove.

In another preferred embodiment, two of R₇, R₈, R₉, R₁₀ and R₁₁ are —H(e.g. R₈ and R₁₀), and the other three of R₇, R₈, R₉, R₁₀ and R₁₁ (e.g.R₇, R₉ and R₁₁) are selected from the group consisting of C₁₋₅-alkyl,—O—C₁₋₅-alkyl and —N(C₁₋₅-alkyl)₂, such as -Me, -Et, —Pr (n- or i-), -Bu(n-, i- or t-), —OMe, —OEt, —OPr (n- or i-), —OBu (n-, i- or t-), —NMe₂,—NEt₂, —N(n-Pr)₂ or —N(i-Pr)₂, for example, -Me, -Et, -n-Pr, -i-Pr,—OMe, —OEt, —O-n-Pr, —O-i-Pr, —NMe₂, —NEt₂. In a particularly preferredembodiment, R₉ and R₁₀ are —H, and R₇, R₉ and R₁₁ are independentlyselected from —C₁₋₅-alkyl groups, such as those described above. In anespecially preferred embodiment, R₉ and R₁₀ are —H, and R₇, R₉ and R₁₁are -i-Pr.

In one embodiment, the monodentate tertiary phosphine ligand is selectedfrom the group consisting of:

R₁/R₃ or R₂/R₃ may form a ring structure with the atoms to which theyare attached and in this instance R₄/R₅, R₅/R₆, R₇/R₈, R₈/R₉, R₉/R₁₀ orR₁₀/R₁₁ independently form a ring structure with the carbon atoms towhich they are attached or R₁, R₂, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁are as defined above. The pair or pairs are selected up to thelimitations imposed by stability and the rules of valence.

The linking group for R₁/R₃ or R₂/R₃ may be a substituted orunsubstituted alkyl, substituted or unsubstituted alkoxy, or substitutedor unsubstituted heteroalkyl. The ring structure formed from the pair orpairs selected from the group consisting of R₄/R₅, R₅/R₆, R₇/R₈, R₈/R₉,R₉/R₁₀ and R₁₀/R₁₁ may be a substituted or unsubstituted cycloalkyl,substituted or unsubstituted heterocycloalkyl, substituted orunsubstituted aryl or substituted or unsubstituted heteroaryl group. R₁and R₂ may be independently selected from the groups defined above whenthey do not form a ring structure with R₃.

In one embodiment, R₄, R₅ and R₆ are —H and the pair R₁/R₃ or R₂/R₃forms a ring structure with the atoms to which they are attached. Inanother embodiment, R₄, R₅ and R₆ are —H and the pair R₁/R₃ or R₂/R₃forms a ring structure with the atoms to which they are attached. Ineither of these instances, R₇/R₈, R₈/R₉, R₉/R₁₀ or R₁₀/R₁₁ mayindependently form a ring structure with the carbon atoms to which theyare attached or R₇, R₈, R₉, R₁₀ and R₁₁ are as defined above. R₁/R₃ orR₂/R₃ may form a ring structure selected from the group consisting of:

wherein:R₁ and R₂ are as defined above: andR′ and R″ are independently as defined above for R₁ and R₂.

In one embodiment, R′ and R″ are independently selected from the groupconsisting of methyl, propyl (n- or i-), butyl (n-, i- or t-),cyclohexyl or phenyl.

Examples of phosphorus ligands include those described by Tang et al,Angew. Chem. Int. Ed. 2010, 49, 5879-5883, Zhao et al, Chem. Eur. J,2013, 19(7), 2261-2265 and Xu et al, Journal of the American ChemicalSociety, 2014, 136(2), 570-573 such as:

It will be understood that, in the depictions herein, where -Me or-^(i)Pr is connected by a wavy line

), either stereoisomer may be present.

The Pd atom in the complex of formula (1) is coordinated to anoptionally substituted ally) group. R₁₂ is an organic group having 1-20carbon atoms, preferably 1-10 carbon atoms and more preferably 1-8carbon atoms. R₁₂ is selected up to the limitations imposed by stabilityand the rules of valence. The number of R₁₂ groups ranges from 0 to 5i.e. m is 0, 1, 2, 3, 4 or 5. When m is 2, 3, 4 or 5, each of R₁₂ may bethe same or different. In certain embodiments, when m is 2, 3, 4, or 5,each R₁₂ is the same. In certain embodiments, m is 0 i.e. the ally)group is unsubstituted. In certain embodiments, m is 1. In certainembodiments, m is 2, wherein each R₁₂ is the same or different.

R₁₂ may be selected from the group consisting of substituted andunsubstituted straight-chain alkyl, substituted and unsubstitutedbranched-chain alkyl, substituted and unsubstituted cycloalkyl,substituted and unsubstituted aryl, and substituted and unsubstitutedheteroaryl wherein the heteroatoms are independently selected fromsulfur, nitrogen and oxygen. In one embodiment, R₁₂ is selected from thegroup consisting of substituted and unsubstituted straight-chain alkyl,substituted and unsubstituted branched-chain alkyl, and substituted andunsubstituted cycloalkyl. In another embodiment, R₁₂ is selected fromthe group consisting of substituted and unsubstituted aryl, andsubstituted and unsubstituted heteroaryl wherein the heteroatoms areindependently selected from sulfur, nitrogen and oxygen. R₁₂ may besubstituted or unsubstituted branched- or straight-chain alkyl groupssuch as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl,sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl,dodecyl or stearyl, cycloalkyl groups such as cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl or adamantyl or aryl groups such as phenyl,naphthyl or anthracyl. In one embodiment, the alkyl groups may beoptionally substituted with one or more (e.g. 1, 2, 3, 4, or 5)substituents each of which may be the same or different such as halide(F, Cl, Br or I), alkoxy groups, e.g. methoxy, ethoxy or propoxy. Thearyl group may be optionally substituted with one or more (e.g. 1, 2, 3,4, or 5) substituents each of which may be the same or different such ashalide (F, Cl, Br or I), straight- or branched-chain alkyl (e.g.C₁-C₁₀), alkoxy (e.g. C₁-C₁₀ alkoxy), straight- or branched-chain(dialkyl)amino (e.g. C₁-C₁₀ dialkyl)amino), heterocycloalkyl (e.g. C₃₋₁₀heterocycloalkyl groups, such as morpholinyl and piperadinyl) ortri(halo)methyl (e.g. F₃C—). Suitable substituted aryl groups includebut are not limited to 2-, 3- or 4-dimethylaminophenyl, 2-, 3- or4-methylphenyl, 2,3- or 3,5-dimethylphenyl, 2-, 3- or 4-methoxyphenyland 4-methoxy-3,5-dimethylphenyl. Substituted or unsubstitutedheteroaryl groups such as pyridyl may also be used. In one embodiment,each R₁₂ is independently a methyl, phenyl or substituted phenyl group.

Suitable optionally substituted ally) groups as coordinated to the Pdatom are shown below:

In the complex of formula (1), X is a coordinated anionic ligand i.e.the anionic ligand is bonded to the Pd atom within the coordinationsphere. In one embodiment, X is a halo group, preferably, Cl, Br, I, andmore preferably, Cl. In another embodiment, X is trifluoroacetate (i.e.F₃CCO₂ ⁻).

The complex of formula (1) may be selected from the group consisting of:

In another aspect, the present invention provides a palladium complex offormula (2):

wherein:R₁₈ and R₁₉ are independently selected from the group consisting of -Me,-Et, —^(n)Pr, —^(i)Pr, —^(n)Bu, —^(i)Bu, cyclohexyl and cycloheptyl;R₁₂ is an organic group having 1-20 carbon atoms;R₂₀, R₂₁, R₂₂, R₂₃ and R₂₄ are independently —H or organic groups having1-20 carbon atoms; orone or both pairs selected from R₂₀/R₂₁ or R₂₂/R₂₃ may independentlyform a ring structure with the atoms to which they are attached;m is 0, 1, 2, 3, 4 or 5; andX is a coordinating anionic ligand.

The complex of formula (2) is a palladium(II) complex comprising amonodentate bi-heteroaryl tertiary phosphine ligand, a coordinatinganionic ligand and an optionally substituted π-allyl group.

R₁₂, m and X are as described above.

R₁₈ and R₁₉ are independently selected from the group consisting of -Me,-Et, —^(n)Pr, —^(i)Pr, —^(n)Bu, —^(i)Bu and cyclohexyl. R₁₈ and R₁₉ areselected up to the limitations imposed by stability and the rules ofvalence. R₁₈ and R₁₉ may the same. Alternatively, R₁₈ and R₁₉ maydifferent. In one preferred embodiment, R₁₈ and R₁₉ are the same and arecyclohexyl groups.

R₂₀, R₂₁, R₂₂, R₂₃ and R₂₄ are independently —H or organic groups having1-20 carbon atoms. R₂₀, R₂₁, R₂₂, R₂₃ and R₂₄ are selected up to thelimitations imposed by stability and the rules of valence. R₂₀ and R₂₁may be independently selected from the group consisting of —H,substituted and unsubstituted straight-chain alkyl, substituted andunsubstituted branched-chain alkyl, substituted and unsubstitutedcycloalkyl, substituted and unsubstituted alkoxy, substituted andunsubstituted aryl, substituted and unsubstituted heteroaryl,substituted and unsubstituted —N(alkyl)₂ (wherein the alkyl groups maybe the same or different and are independently selected fromstraight-chain or branched-chain groups), substituted and unsubstituted—N(cycloalkyl)₂ (wherein the cycloalkyl groups may be the same ordifferent), substituted and unsubstituted —N(aryl)₂ (wherein the arylgroups may be the same or different), substituted and unsubstituted—N(heteroaryl)₂ (wherein the heteroaryl groups may be the same ordifferent) and substituted and unsubstituted heterocycloalkyl groups.The heteroatoms in the heteroaryl or heterocycloalkyl groups may beindependently selected from sulfur, nitrogen or/and oxygen. In oneembodiment, the alkyl groups may be optionally substituted with one ormore (e.g. 1, 2, 3, 4, or 5) substituents each of which may be the sameor different such as halide (F, Cl, Br or I) e.g. —CF₃, alkoxy groups,e.g. methoxy, ethoxy or propoxy. The aryl group may be optionallysubstituted with one or more (e.g. 1, 2, 3, 4, or 5) substituents eachof which may be the same or different such as halide (F, Cl, Br or I),straight- or branched-chain alkyl (e.g. C₁-C₁₀), alkoxy (e.g. C₁-C₁₀alkoxy), straight- or branched-chain (dialkyl)amino (e.g. C₁-C₁₀dialkyl)amino), heterocycloalkyl (e.g. C₃₋₁₀ heterocycloalkyl groups,such as morpholinyl and piperadinyl) or tri(halo)methyl (e.g. F₃C—).Suitable substituted aryl groups include but are not limited to 2-, 3-or 4-dimethylaminophenyl, 2-, 3- or 4-methylphenyl, 2,3- or3,5-dimethylphenyl, 2-, 3- or 4-methoxyphenyl and4-methoxy-3,5-dimethylphenyl. Substituted or unsubstituted heteroarylgroups such as pyridyl may also be used. Suitable unsubstituted—N(alkyl)₂ groups include but are not limited to —NMe₂, —NEt₂ and —NPr₂(n- or i-). A suitable unsubstituted —N(cycloalkyl)₂ group includes butis not limited to —N(Cy)₂. Suitable substituted —N(alkyl)₂ groupsinclude but are not limited to —N(CH₂CH₂OMe)₂ and —N(CF₃)₂. Suitableunsubstituted —N(aryl)₂ groups include but are not limited to —NPh₂.Suitable substituted —N(aryl)₂ groups include but are not limited to—N(2-, 3- or 4-dimethylaminophenyl)₂, —N(2-, 3- or 4-methylphenyl)₂,—N(2,3- or 3,5-dimethylphenyl)₂, —N(2-, 3- or 4-methoxyphenyl)₂ and—N(4-methoxy-3,5-dimethylphenyl)₂. Suitable unsubstituted—N(heteroaryl)₂ groups include but are not limited to —N(furyl)₂ and—N(pyridyl)₂. Substituted and unsubstituted heterocycloalkyl groupsinclude C₄₋₈-heterocycloalkyl groups, such as piperidinyl andmorpholinyl.

In one preferred embodiment, both of R₂₀ and R₂₁ are —H.

R₂₂ and R₂₄ may be independently selected from the group consisting of—H, substituted and unsubstituted straight-chain alkyl, substituted andunsubstituted branched-chain alkyl, substituted and unsubstitutedcycloalkyl, substituted and unsubstituted alkoxy, substituted andunsubstituted-thioalkyl, substituted and unsubstituted aryl, substitutedand unsubstituted heteroaryl, substituted and unsubstituted —N(alkyl)₂(wherein the alkyl groups may be the same or different and areindependently selected from straight-chain or branched-chain groups),substituted and unsubstituted —N(cycloalkyl)₂ (wherein the cycloalkylgroups may be the same or different), substituted and unsubstituted—N(aryl)₂ (wherein the aryl groups may be the same or different),substituted and unsubstituted —N(heteroaryl)₂ (wherein the heteroarylgroups may be the same or different). The heteroatoms in the heteroarylgroups may be independently selected from sulfur, nitrogen or/andoxygen. In one embodiment, the alkyl groups may be optionallysubstituted with one or more (e.g. 1, 2, 3, 4, or 5) substituents suchas halide (F, Cl, Br or I), alkoxy groups, e.g. methoxy, ethoxy orpropoxy. The aryl group may be optionally substituted with one or more(e.g. 1, 2, 3, 4, or 5) substituents such as halide (F, Cl, Br or I),straight- or branched-chain alkyl (e.g. C₁-C₁₀), alkoxy (e.g. C₁-C₁₀alkoxy), straight- or branched-chain (dialkyl)amino (e.g. C₁-C₁₀dialkyl)amino), heterocycloalkyl (e.g. C₃₋₁₀ heterocycloalkyl groups,such as morpholinyl and piperadinyl) or tri(halo)methyl (e.g. F₃C—).Suitable substituted aryl groups include but are not limited to 2-, 3-or 4-dimethylaminophenyl, 2-, 3- or 4-methylphenyl, 2,3- or3,5-dimethylphenyl, 2-, 3- or 4-methoxyphenyl and4-methoxy-3,5-dimethylphenyl. Substituted or unsubstituted heteroarylgroups such as pyridyl may also be used. Substituted orunsubstituted-thioalkyl groups include —S(C₁₋₅-alkyl), such as —SMe,-SEt, —SPr (n- or i-). In one embodiment, both of R₂₂ and R₂₄ arephenyl.

R₂₃ may be independently selected from the group consisting of —H,substituted and unsubstituted straight-chain alkyl, substituted andunsubstituted branched-chain alkyl, substituted and unsubstitutedcycloalkyl, substituted and unsubstituted alkoxy, substituted andunsubstituted aryl, and substituted and unsubstituted heteroaryl. Theheteroatoms in the heteroaryl groups may be independently selected fromsulfur, nitrogen or/and oxygen. In one embodiment, the alkyl groups maybe optionally substituted with one or more (e.g. 1, 2, 3, 4, or 5)substituents such as halide (F, Cl, Br or I), alkoxy groups, e.g.methoxy, ethoxy or propoxy. The aryl group may be optionally substitutedwith one or more (e.g. 1, 2, 3, 4, or 5) substituents such as halide (F,Cl, Br or I), straight- or branched-chain alkyl (e.g. C₁-C₁₀), alkoxy(e.g. C₁-C₁₀ alkoxy), straight- or branched-chain (dialkyl)amino (e.g.(C₁-C₁₀ dialkyl)amino), heterocycloalkyl (e.g. C₃₋₁₀ heterocycloalkylgroups, such as morpholinyl and piperadinyl) or tri(halo)methyl (e.g.F₃C—). Suitable substituted aryl groups include but are not limited to2-, 3- or 4-dimethylaminophenyl, 2-, 3- or 4-methylphenyl, 2,3- or3,5-dimethylphenyl, 2-, 3- or 4-methoxyphenyl and4-methoxy-3,5-dimethylphenyl. Substituted or unsubstituted heteroarylgroups such as pyridyl may also be used. In one embodiment, R₂₃ isphenyl.

In one preferred embodiment, each of R₂₂, R₂₃ and R₂₄ are phenyl groups.

In one embodiment, the monodentate bi-heteroaryl tertiary phosphineligand is selected from the group consisting of:

The complex of formula (2) may be selected from the group consisting of:

The complex of formula (1) or the complex of formula (2) may be preparedin a process comprising the step of reacting a complex of formula (3)with a monodentate biaryl ligand of formula (4) or a monodentatebi-heteroaryl tertiary phosphine ligand of formula (5) to form thecomplex of formula (1) or the complex of formula (2),

wherein,R₁ and R₂ are independently organic groups having 1-20 carbon atoms, orR₁ and R₂ are linked to form a ring structure with E;R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are independently —H or organicgroups having 1-20 carbon atoms; orone or more pairs selected from R₁/R₃, R₂/R₃, R₃/R₄, R₄/R₅, R₅/R₆,R₇/R₈, R₈/R₉, R₉/R₁₀ or R₁₀/R₁₁ independently may form a ring structurewith the atoms to which they are attached;R₁₂ is an organic group having 1-20 carbon atoms;R₁₈ and R₁₉ are independently selected from the group consisting of -Me,-Et, —^(n)Pr, —^(i)Pr, —^(n)Bu, —^(i)Bu, cyclohexyl and cycloheptyl;R₂₀, R₂₁, R₂₂, R₂₃ and R₂₄ are independently —H or organic groups having1-20 carbon atoms; or one or both pairs selected from R₂₀/R₂₁ or R₂₂/R₂₃independently may form a ring structure with the atoms to which they areattached;m is 0, 1, 2, 3, 4 or 5;E is P or As; andX is a coordinating anionic ligand;provided that the palladium complex of formula (1) is not(π-crotyl)PdCl(dicyclohexylphosphino-2-biphenyl).

R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₈, R₁₉, R₂₀, R₂₁,R₂₂, R₂₃ and R₂₄, m, E and X are as described above.

One or more pairs (e.g. 1, 2 or 3 pairs) selected from R₁/R₃, R₂/R₃,R₃/R₄, R₄/R₅, R₅/R₆, R₇/R₈, R₈/R₉, R₉/R₁₀ or R₁₀/R₁₁ may independentlyform a ring structure with the atoms to which they are attached. Thepair or pairs are selected up to the limitations imposed by stabilityand the rules of valence. The ring structure may be a substituted orunsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl,substituted or unsubstituted aryl or substituted or unsubstitutedheteroaryl group.

If R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ or R₁₁ does not form part ofa pair, the groups are as described above.

R₁/R₃ or R₂/R₃ may form a ring structure with the atoms to which theyare attached and in this instance R₄/R₅, R₅/R₆, R₇/R₈, R₈/R₉, R₉/R₁₀ orR₁₀/R₁₁ independently form a ring structure with the carbon atoms towhich they are attached or R₁, R₂, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁are as defined above. R₁ and R₂ may be independently selected from thegroups defined above when they do not form a ring structure with R₃.

The linking group for R₁/R₃ or R₂/R₃ may be a substituted orunsubstituted alkyl, substituted or unsubstituted alkoxy, or substitutedor unsubstituted heteroalkyl. The ring structure formed from the pair orpairs selected from the group consisting of R₄/R₅, R₅/R₆, R₇/R₈, R₈/R₉,R₉/R₁₀ and R₁₀/R₁₁ may be a substituted or unsubstituted cycloalkyl,substituted or unsubstituted heterocycloalkyl, substituted orunsubstituted aryl or substituted or unsubstituted heteroaryl group. R₁and R₂ may be independently selected from the groups defined above whenthey do not form a ring structure with R₃.

In one embodiment, R₄, R₅ and R₆ are —H and the pair R₁/R₃ or R₂/R₃forms a ring structure with the atoms to which they are attached. Inanother embodiment, R₄, R₅ and R₆ are —H and the pair R₁/R₃ or R₂/R₃forms a ring structure with the atoms to which they are attached. Ineither of these instances, R₇/R₈, R₈/R₉, R₉/R₁₀ or R₁₀/R₁₁ mayindependently form a ring structure with the carbon atoms to which theyare attached or R₇, R₈, R₉, R₁₀ and R₁₁ are as defined above. R₁/R₃ orR₂/R₃ may form a ring structure selected from the group consisting of:

whereinR₁ and R₂ are as defined above: andR′ and R″ are independently as defined above for R₁ and R₂.

In one embodiment, R′ and R″ are independently selected from the groupconsisting of methyl, propyl (n- or i-), butyl (n-, i- or t-),cyclohexyl or phenyl.

In another embodiment, R₉ is —H and the pairs R₇/R₈ and R₁₀/R₁₁ form aring structure with the atoms to which they are attached. Each pair mayform a substituted or unsubstituted aryl ring (for example, a phenylring) together with the carbon atoms to which they are attached.

Examples of phosphorus ligands include those described by Tang et al,Angew. Chem. Int. Ed. 2010, 49, 5879-5883, Zhao et al, Chem. Eur. J,2013, 19(7), 2261-2265 and Xu et al, Journal of the American ChemicalSociety, 2014, 136(2), 570-573 such as:

It will be understood that, in the depictions herein, where -Me or —Pris connected by a wavy line (

), either stereoisomer may be present.

In one embodiment, R₅ and R₆ form a substituted or unsubstituted arylring, preferably a phenyl ring, together with the carbon atoms to whichthey are attached. In another embodiment, R₇ and R₈ form a substitutedor unsubstituted aryl ring, preferably a phenyl ring, together with thecarbon atoms to which they are attached. An example is representedbelow:

Without wishing to be bound by theory, it is believed that the complexesof formula (1) can be prepared as a result of balancing the steric bulkof groups R₁ and R₂ with the steric bulk of groups R₇, R₈, R₉, R₁₀and/or R₁₁. For example, in the complex of formula (1), when E is P, R₁and R₂ may be selected to be more sterically bulky than a cyclohexylgroup (for example a tert-butyl group) when the substituents R₇, R₈, R₉,R₁₀ and/or R₁₁ are selected to be less sterically bulky (for example H).Similarly, R₁ and R₂ are typically selected to be less sterically bulky(for example a cyclohexyl group or smaller) when the substituents R₇,R₈, R₉, R₁₀ and/or R₁₁ are selected to be more sterically bulky (forexample methoxy, iso-propyl, dimethylamino).

The complex of formula (3) may be prepared according to known methods(see, for example, a) Marion, N.: Navarro, O.; Mei, J.; Stevens, E. D.;Scott, N. M.; Nolan, S. P. J. Am. Chem. Soc. 2006, 128, 4101. b) Auburn,P. R.; Mackenzie, P. B.; Bosnich, B. J. Am. Chem. Soc. 1985, 107, 2033.c) Dent, W. I.; Long, R.; Wilkinson, G. J. Chem. Soc. 1964, 1585. d)Nicholson, J. K.; Powell, J.; Shaw, B. L. J. Chem. Soc.; Chem. Commun.1966, 174) each of which is incorporated herein by reference in itsentirety for all purposes. Suitable complexes of formula (3) include:

In one embodiment, the process comprises the step of reacting thecomplex of formula (3) with the monodentate ligand of formula (4) toform the complex of formula (1). In another embodiment, the processcomprises the step of reacting the complex of formula (3) with themonodentate bi-heteroaryl phosphine ligand of formula (5) to form thecomplex of formula (2).

The complex of formula (3) and the ligand (4) or (5) may be combined ina solvent. In this case, the solvent is any suitable aprotic solvent orcombination of aprotic solvents. Examples of aprotic solvents aretoluene, benzene, tetrahydrofuran (THF), 2-methyltetrahydrofuran,dichloromethane (DCM), dioxane, acetone, acetonitrile, dimethylformamide(DMF), N-methylpyrrolidine (NMP), dimethylacetamide (DMAc),methyltertbutylether (MTBE), diethylether, hexane, heptane, pentane orethylacetate. Preferred solvents are THF, 2-methyltetrahydrofuran,toluene, DCM or a combination thereof. The solvent may be anhydrous. Theconcentration of the complex of formula (3) in the solvent is preferablyabout 0.001 mol/L to about 3.00 mol/L and more preferably, about 0.03mol/L to about 2.50 mol/L.

Any suitable quantity of ligand may be used, although it is preferredthat the molar ratio of the complex of formula (3): ligand is from about1:1 to about 1:15, such as about 1:1 to about 1:11. In one embodiment,the molar ratio of complex of formula (3): ligand about 1:1.90 to about1:2.30.

The reaction is preferably carried out under an inert atmosphere, suchas nitrogen or argon.

The process of the invention may be carried out at a temperature in therange of about −10° C. to about 60° C., preferably about 0° C. to about35° C. and more preferably at about room temperature (rt) (i.e. about20° C. to about 30° C.). It is preferred that the temperature ismaintained below the decomposition temperature and so when the complexesof formula (1), (2) or (3) are known to decompose within the temperatureranges given above, the temperature should be maintained below thedecomposition temperature.

The reaction may be carried out for a period of from about severalminutes to about 24 hours. Usually the reaction is complete within about6 hours for a laboratory scale reaction. On completion, a proportion ofthe solvent may be evaporated if desired prior to recovery of thecomplex. Furthermore, if desired an anti-solvent (e.g. an alkane, suchas pentane or hexane) may be used to precipitate the complex from thesolvent. The complex product may be recovered directly by filtering,decanting or centrifuging.

Howsoever the complex is recovered, the separated complex may be washedand then dried. Drying may be performed using known methods, for exampleat temperatures in the range 10-60° C. and preferably 20-40° C. under1-30 mbar vacuum for 1 hour to 5 days. If desired the complex may berecrystallised.

In certain embodiments, the complexes may be prepared in high yield. Incertain embodiments, the complexes may be prepared having a high purity.In certain embodiments, the complexes are highly active catalysts. Incertain embodiments, the complexes are stable to air and moisture atambient temperatures. A number of complexes (for example,(π-allyl)Pd(CyBippyPhos)Cl, (π-allyl)Pd(SPhos)Cl, (π-allyl)Pd(XPhos)Cl,(π-allyl)Pd(RuPhos)Cl, (π-allyl)Pd(BrettPhos)Cl, (π-crotyl)Pd(XPhos)Cl,(π-crotyl)Pd(SPhos)Cl, (π-crotyl)Pd(RuPhos)Cl, (π-cinnamyl)Pd(SPhos)Cland (π-cinnamyl)Pd(RuPhos)Cl) were tested for storage stability andshowed substantially no decomposition as judged by ³¹P NMR under normalstorage conditions for 1-2 years. Normal storage conditions refers tostorage in air under normal moisture conditions (i.e. not in a gloveboxor desiccator). Application studies of the complexes indicate that theymay be easily activated under mild conditions. For example, ally)complexes may be typically activated at >60° C., and the crotyl andcinnamyl complexes may be activated readily at room temperature. Ifdesired, however, the complexes of the present invention may be used inreactions at higher temperatures (for example, ≥about 60° C. to about≤about 150° C.).

Without wishing to be bound by theory, it is believed that the complexesactivate to form an LPd(0) species (L=phosphine ligand). Relativelybenign substituted olefin by-products may also be produced on activationof the complexes. An example of an olefin by-product is shown below fora particular π-allyl complex where m is 1.

Without wishing to be bound by theory, it is also believed that theactivity observed by the complexes of the present invention may be as aresult of suppressing the formation of stable non-reactive(μ-(R₁₂)_(m)-allyl)Pd₂(L)₂(μ-Cl) dimers. In this respect, the active“LPd(0)” species may be consumed by comproportionation with the yetunreacted complex of formula (1) or (2) to form the dimer complexes. Thesuppression of the comproportionation process may be caused by the dimercomplexes becoming increasingly destabilized with increasing ligand sizeand/or substitution on the ally) group due to steric strain, therebyretarding their propensity to form. Additionally, the fast rate ofoxidative addition that the complexes of the invention exhibit shouldrapidly draw the active L-Pd(0) into the catalytic cycle, thus,disfavouring the non-productive comproportionation process. Thesemechanisms are illustrated below for a particular π-ally) complex whereL is a ligand of formula (4) or (5), X is chloro and m is 1.

The catalysts of the present invention may be used for carbon-carboncoupling reactions. Examples of carbon-carbon coupling reactions includeHeck, Suzuki, Sonogashira or Negishi reactions, ketone α-arylationreactions, aldehyde α-arylation reactions, allylic substitutionreactions and trifluoromethation reactions. The catalysts of the presentinvention may also be used for carbon-heteroatom coupling reactions,such as carbon-nitrogen coupling reactions (i.e. Buchwald-Hartwigreaction), or carbon-oxygen or carbon-sulfur coupling reactions.

In another aspect, therefore, the present invention provides a processfor carrying out a carbon-carbon coupling reaction in the presence of acatalyst, the process comprising:

(a) the use of a complex of formula (1):

whereinR₁ and R₂ are independently organic groups having 1-20 carbon atoms, orR₁ and R₂ are linked to form a ring structure with E;R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are independently —H or organicgroups having 1-20 carbon atoms; orR₁/R₃ or R₂/R₃ forms a ring structure with the atoms to which they areattached and in this instance R₄/R₅, R₅/R₆, R₇/R₈, R₈/R₉, R₉/R₁₀ orR₁₀/R₁₁ may independently form a ring structure with the carbon atoms towhich they are attached or R₁, R₂, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁are as defined above;R₁₂ is an organic group having 1-20 carbon atoms;m is 0, 1, 2, 3, 4 or 5;E is P or As; andX is a coordinating anionic ligand;or:(b) a complex of formula (2) as defined in any one of claims 17 to 24.

The complex of formula (1), the complex of formula (2), R₁, R₂, R₃, R₄,R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₈, R₁₉, R₂₀, R₂₁, R₂₂, R₂₃ and R₂₄,m, E and X are as described above.

In one embodiment, the process comprises the use of a complex of formula(1) as defined in any one of claims 1 to 16. In another embodiment, theprocess comprises the use of the complex of formula (2) as defined inany one of claims 17 to 24.

In another aspect, the invention provides a process for carrying out acarbon-heteroatom coupling reaction in the presence of a catalyst, theprocess comprising:

(a) the use of a complex of formula (1):

wherein:R₁ and R₂ are independently organic groups having 1-20 carbon atoms, orR₁ and R₂ are linked to form a ring structure with E;R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are independently —H or organicgroups having 1-20 carbon atoms; orR₁/R₃ or R₂/R₃ forms a ring structure with the atoms to which they areattached and in this instance R₄/R₅, R₅/R₆, R₇/R₈, R₈/R₉, R₉/R₁₀ orR₁₀/R₁₁ may independently form a ring structure with the carbon atoms towhich they are attached or R₁, R₂, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁are as defined above;R₁₂ is an organic group having 1-20 carbon atoms;m is 0, 1, 2, 3, 4 or 5;E is P or As; andX is a coordinating anionic ligand;or:(b) a complex of formula (2) as defined in any one of claims 17 to 24.

The complex of formula (1), the complex of formula (2), R₁, R₂, R₃, R₄,R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₈, R₁₉, R₂₀, R₂₁, R₂₂, R₂₃, R₂₄, m,E and X are as described above.

In one embodiment, the process comprises the use of a complex of formula(1) as defined in any one of claims 1 to 16. In another embodiment, theprocess comprises the use of the complex of formula (2) as defined inany one of claims 17 to 24.

In another aspect, the invention provides the use of a complex offormula (1) or a complex of formula (2) as a catalyst in carbon-carboncoupling reactions, wherein:

(a) the complex of formula (1) is:

wherein:R₁ and R₂ are independently organic groups having 1-20 carbon atoms, orR₁ and R₂ are linked to form a ring structure with E;R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are independently —H or organicgroups having 1-20 carbon atoms; orR₁/R₃ or R₂/R₃ forms a ring structure with the atoms to which they areattached and in this instance R₄/R₅, R₅/R₆, R₇/R₈, R₈/R₉, R₉/R₁₀ orR₁₀/R₁₁ may independently form a ring structure with the carbon atoms towhich they are attached or R₁, R₂, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁are as defined above;R₁₂ is an organic group having 1-20 carbon atoms;m is 0, 1, 2, 3, 4 or 5;E is P or As; andX is a coordinating anionic ligand;and:(b) the complex of formula (2) as defined in any one of claims 17 to 24.

The complex of formula (1), the complex of formula (2), R₁, R₂, R₃, R₄,R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₈, R₁₉, R₂₀, R₂₁, R₂₂, R₂₃, R₂₄, m,E and X are as described above.

In one embodiment, the complex of formula (1) is as defined in any oneof claims 1 to 14. In another embodiment, the complex of formula (2) isas defined in any one of claims 17 to 24.

In another aspect, the invention provides the use of a complex offormula (1) or a complex of formula (2) as a catalyst incarbon-heteroatom coupling reactions, wherein:

(a) the complex of formula (1) is:

wherein:R₁ and R₂ are independently organic groups having 1-20 carbon atoms, orR₁ and R₂ are linked to form a ring structure with E;R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are independently —H or organicgroups having 1-20 carbon atoms; orR₁/R₃ or R₂/R₃ forms a ring structure with the atoms to which they areattached and in this instance R₄/R₅, R₅/R₆, R₇/R₈, R₈/R₉, R₉/R₁₀ orR₁₀/R₁₁ may independently form a ring structure with the carbon atoms towhich they are attached or R₁, R₂, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁are as defined above;R₁₂ is an organic group having 1-20 carbon atoms;m is 0, 1, 2, 3, 4 or 5;E is P or As; andX is a coordinating anionic ligand;and:(b) the complex of formula (2) is as defined in any one of claims 17 to24.

The complex of formula (1), the complex of formula (2), R₁, R₂, R₃, R₄,R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₈, R₁₉, R₂₀, R₂₁, R₂₂, R₂₃, R₂₄, m,E and X are as described above.

In one embodiment, the complex of formula (1) is as defined in any oneof claims 1 to 16. In another embodiment, the complex of formula (2) isas defined in any one of claims 17 to 24.

Embodiments and/or optional features of the invention have beendescribed above. Any aspect of the invention may be combined with anyother aspect of the invention, unless the context demands otherwise. Anyof the embodiments or optional features of any aspect may be combined,singly or in combination, with any aspect of the invention, unless thecontext demands otherwise.

The invention will now be described by way of the following non-limitingexamples and with reference to the following figures in which:

FIG. 1 is a ¹H NMR spectrum of Pd(π-allyl)(BrettPhos)Cl.

FIG. 2 is a ¹H NMR spectrum of Pd(π-crotyl)(BrettPhos)Cl.

FIG. 3 is a ¹H NMR spectrum of Pd(π-cinnamyl)(BrettPhos)Cl.

FIG. 4 is a ¹H NMR spectrum of Pd(π-allyl)(JackiePhos)Cl.

FIG. 5 is a ¹H NMR spectrum of (π-crotyl)Pd(CyBippyPhos)Cl.

FIG. 6 illustrates the rate of conversion in the α-arylation ofacetophenone with 4-chloroanisole using (π-allyl)Pd(XPhos)Cl,(π-crotyl)Pd(XPhos)Cl, (π-cinnamyl)Pd(XPhos)Cl, 3^(rd) generation XPhospalladacycle and (π-allyl)Pd(XPhos)Cl with 1 mol % added carbazole.

EXAMPLES

All solvents and reagents were purchased from commercial sources andused as received. All catalysts, ligands or precious metal precursorswere obtained from Johnson Matthey Catalysis or Alfa Aesar. Flashchromatography was performed either on a Teledyne Isco CombiFlashRfusing 12 g RediSepRf silica gel cartridges. ³¹P, ¹H and ¹³C NMR spectrawere recorded on a 400 MHz spectrometer, with chemical shifts reportedrelative to residual solvent as internal references (CDCl₃: 7.26 ppm for¹H NMR and 77.26 ppm for ¹³C NMR, C₆D₆: 7.16 ppm for ¹H NMR and 128.06ppm ¹³C NMR, DMSO-d6: 2.50 ppm for ¹H NMR and 39.52 ppm for ¹³C NMR,toluene-d8: 2.08 ppm for ¹H NMR and 20.43 ppm for ¹³C NMR), unlessotherwise stated, while ³¹P¹H NMR spectra were externally referenced to85% H₃PO₄. The following abbreviations were used to explain themultiplicities: s=singlet, d=doublet, t=triplet, q=quartet,quint=quintet, sept=septet, m=multiplet, b=broad, app t=apparenttriplet, app d=apparent doublet, br=broad. Elemental analyses were sentto Robertson Microlit Laboratories, Inc. All reactions were carried outin individual Schlenk flasks under a nitrogen atmosphere. The purity ofthe isolated products was >95% as determined by ¹H NMR, GC/MS orelemental analysis unless noted otherwise.

Crystallographic data were obtained at 120K on a APEX Bruker-AXS CCDX-ray diffractometer equipped with a monocap collimator. Structures weresolved with SHELXTL software. These data was obtained from University ofDelaware X-ray Crystallography Laboratory of the Department of Chemistryand Biochemistry.

General Procedure for the Preparation of [Pd(Optionally Substituted(R₁₂)_(n)-Allyl)(X)]₂ Complexes:

Distilled H₂O in a three-necked roundbottom flask is purged withnitrogen for 30 minutes. PdCl₂ and KCl are subsequently added to theflask and the solution is stirred at room temperature for 1 h. Then,optionally substituted (R₄)_(n)-allyl chloride is added and theresulting reaction mixture is stirred at room temperature overnight(18-20 hrs). The reaction is extracted with chloroform, and the aqueouslayer washed with chloroform three times. The organic layers arecombined, dried over MgSO₄, filtered and concentrated in vacuo. Thecrude product is recrystallised from chloroform and methyl tert-butylether, and the resulting solid is isolated by filtration and dried invacuo.

[Pd(π-cinnamyl)Cl]₂

PdCl₂ (590 mg, 3.33 mmol); KCl (473 mg, 6.67 mmol); cinnamyl chloride(1.39 mL, 9.99 mmol); H₂O (83 mL). The dimer is obtained as a yellowsolid.

[Pd(π-1-crotyl)Cl]₂

PdCl₂ (590 mg, 3.33 mmol); KCl (473 mg, 6.67 mmol); crotyl chloride(0.97 mL, 9.99 mmol); H₂O (83 mL). The dimer is obtained as a yellowsolid.

[Pd(π-prenyl)Cl]₂

PdCl₂ (590 mg, 3.33 mmol); KCl (473 mg, 6.67 mmol);1-chloride-3-methyl-2-butene (1.13 mL, 9.99 mmol); H₂O (83 mL). Thedimer is obtained as a yellow solid.

[Pd(π-methallyl)Cl]₂

PdCl₂ (590 mg, 3.33 mmol); KCl (473 mg, 6.67 mmol);3-chloride-2-methyl-1-propene (0.98 mL, 9.99 mmol); H₂O (83 mL). Thedimer is obtained as a yellow solid (269 mg, 41%).

Example 1 (According to the Invention) Representative Procedure for thePreparation of [Pd(Optionally Substituted (R₁₂)_(m)-Allyl)(Ligand)(X)Complexes

A dry Schlenk tube is charged with the ligand (4.74 mmol) and[(optionally substituted (R₁₂)_(m)-allyl)PdCl]₂ (2.36 mmol). The tube isevacuated and backfilled with nitrogen a total of three times. 10 mL ofanhydrous solvent (such as THF or toluene) is added and the mixture isstirred at room temperature for a period of time (e.g. 20 minutes).Pentane (5 mL) or hexanes is added to fully precipitate the product. Theproduct is collected by vacuum filtration, washed (3×10 mL of pentane,or hexanes) and dried under vacuum.

Pd(π-allyl)(JohnPhos)Cl

Following the representative procedure: [(allyl)PdCl]₂ (1.00 g, 2.75mmol); JohnPhos (1.64 g, 5.50 mmol); toluene (13.2 mL); 1 h. Productobtained as a pale yellow solid (2.46 g, 93%); ¹H NMR (400 MHz, CDCl₃,δ): 7.93-7.82 (m, 1H), 7.71-7.57 (m, 2H), 7.50-7.19 (m, 6H), 4.85-2.60(m, 5H), 1.90-1.10 (m, 18H); ¹³C NMR (100 MHz, CDCl₃, δ): 149.0, 148.8,142.2 (2 peaks), 134.8, 134.6, 133.6 (2 peaks), 130.4, 129.8, 129.7,129.6, 128.1, 126.3, 125.4, 125.3, 113.3, 113.2, 81.7 (br), 57.6 (br),37.2, 30.9 [Observed complexity due to C—P coupling]; ³¹P NMR (162 MHz,CDCl₃, δ): 57.3; Anal. calcd. for C₂₃H₃₂ClPPd: C, 57.39; H, 6.70. FoundC, 57.35; H, 6.53.

(π-crotyl)Pd(JohnPhos)Cl

A dry Schlenk flask equipped with a Teflon-coated magnetic stir bar ischarged with 1.00 g (2.54 mmol) of [(crotyl)PdCl]₂ (0.50 equiv) followedby 1.52 g (5.08 mmol) of JohnPhos. The flask is fitted with a rubberseptum and it is evacuated and backfilled with nitrogen. Thisevacuation/nitrogen backfill cycle is repeated two additional times.Solvent (anhydrous toluene) is added via syringe and the react ionmixture is stirred at rt for 1.25 hours. Pentane (25 mL) is then addedto fully precipitate the product. The solid materials are then collectedby suction filtration, washed with additional pentane (or hexanes), anddried in vacuo to give 2.40 g (4.84 mmol, 95%) of the title compound asa yellow solid. ¹H NMR (400 MHz, CDCl₃, δ): 7.87 (s, 1H), 7.50-7.75 (m,2H), 7.10-7.50 (m, 6H), 3.98-4.23 (m, 1H), 3.60-3.83 (m, 1H), 2.99-3.11(m, 1H), 1.20-1.76 (m, 22H). ¹³C NMR (101 MHz, CDCl₃, δ): 149.0, 148.8,142.1 (2 peaks), 135.0, 133.9 (2 peaks), 130.4, 130.0, 129.8, 129.7,127.9, 126.4, 125.2 (2 peaks), 112.7 (2 peaks), 100.3, 100.0, 52.2,37.7, 37.6, 37.3, 37.2, 31.7, 31.6, 30.5, 30.4, 17.7, 17.6 [Observedcomplexity due to C—P coupling].

³¹P NMR (162 MHz, CDCl₃, δ): 57.1.

Anal. Calcd. for C₂₄H₃₄ClPPd: C, 58.19; H, 6.92. Found: C, 57.91; H,6.74.

Pd(π-allyl)(SPhos)Cl

Following the representative procedure: [(allyl)PdCl]₂ (505 mg, 1.39mmol); SPhos (1.14 g, 2.78 mmol); THF (3 mL); 6 h. Product obtained as awhite solid (1.30 g, 79%); ¹H NMR (400 MHz, CDCl₃, δ): 7.65 (t, J=8.6Hz, 1H), 7.42 (t, J=7.4 Hz, 1H), 7.33 (t, J=7.8 Hz, 1H), 7.30-7.22 (m,1H), 7.06 (dd, J=3.5 Hz, 8.2 Hz, 1H), 6.70-6.44 (m, 2H), 5.24-5.08 (m,1H), 4.47 (t, J=7.1 Hz, 1H), 3.82-3.60 (m, 6H), 3.40-3.22 (m, 1H), 3.02(dd, J=9.4 Hz, 13.7 Hz, 1H), 2.41-2.00 (m, 3H), 2.00-0.90 (m, 20H); ¹³CNMR (100 MHz, CDCl₃, δ): 158.0, 140.6, 140.5, 134.8, 134.7, 133.0,132.9, 131.3, 131.0, 129.5, 128.9, 125.9, 125.8, 119.4, 119.4, 115.9,115.8, 109.9, 104.2, 103.1, 82.2, 81.9, 55.4, 54.7, 36.2 (4 peaks),29.8, 29.0, 27.3, 27.2, 26.1 [Observed complexity due to C—P coupling];³¹P NMR (162 MHz, CDCl₃, δ): 31.8; Anal. calcd. for C₂₉H₄₀O₂ClPPd: C,58.67; H, 6.79. Found C, 58.93; H, 6.76.

Single crystals of Pd(π-allyl)(SPhos)Cl are obtained by slow cooling ofa 1:1 THF/pentane solution in the freezer.

Pd (π-crotyl) (SPhos)Cl

Following the representative procedure: [(crotyl)PdCl]₂ (501 mg, 1.27mmol); SPhos (1.05 g, 2.56 mmol); THF (5 mL); 6 h. Product obtained asan off-white solid (1.28 g, 83%); ¹H NMR (400 MHz, C₆D₆, δ): 7.58 (t,J=7.7 Hz, 1H), 7.17-7.04 (m, 4H), 6.42 (d, J=8.5 Hz, 1H), 6.28 (d, J=8.3Hz, 1H), 4.69-4.58 (m, 1H), 3.77-3.62 (m, 1H), 3.53 (s, 3H), 3.25 (s,3H), 3.20 (d, J=6.6 Hz, 1H), 2.52-2.29 (m, 2H), 2.20-1.15 (m, 24H); ¹³CNMR (100 MHz, C₆D₆, δ): 158.0, 157.7, 141.8, 141.7, 133.4 (2 peaks),133.2, 133.1, 132.0, 131.7, 129.1 (2 peaks), 128.2, 125.6, 125.5, 119.8,119.7, 114.1 (2 peaks), 103.7, 102.8, 99.8, 99.6, 54.8, 54.6, 48.4,38.0, 37.8, 37.3, 37.1, 29.9, 28.5, 28.3, 27.4 (2 peaks), 27.3, 27.1,27.0 (2 peaks), 26.9, 26.1, 17.1 (2 peaks) [Observed complexity due toC—P coupling]; ³¹P NMR (162 MHz, C₆D₆, δ): 28.9; Anal. calcd. forC₃₀H₄₂O₂ClPPd: C, 59.31; H, 6.97. Found C, 59.15; H, 7.17

Pd(π-cinnamyl)(SPhos)Cl

Following the representative procedure: [(cinnamyl)PdCl]₂ (1.00 g, 1.93mmol); SPhos (1.59 g, 3.86 mmol); toluene (4.3 mL); 1 h. Productobtained as a yellow solid (2.56 g, 99%); ¹H NMR (400 MHz, CDCl₃, δ):7.68 (t, J=8.5 Hz, 1H), 7.48-7.20 (m, 8H), 7.08-7.02 (m, 1H), 6.60 (d,J=8.3 Hz, 1H), 5.53-5.42 (m, 1H), 4.78-4.67 (m, 1H), 3.67 (s, 6H),3.43-2.20 (m, 4H), 2.01-1.88 (m, 2H), 1.80-1.51 (m, 8H), 1.46-1.05 (m,10H); ¹³C NMR (100 MHz, CDCl₃, δ): 157.8, 140.3, 140.2, 136.9, 136.8,135.0, 134.9, 133.0 (2 peaks), 131.3, 131.0, 129.3, 129.0, 128.4, 128.4,128.1, 127.6 (2 peaks), 127.5, 125.7, 125.6, 119.4 (2 peaks), 109.3,109.2, 103.6, 101.7, 101.4, 55.3, 50.0, 36.1, 35.9, 29.8, 29.7, 29.2,27.3, 27.2, 27.0, 26.9, 26.1 [Observed complexity due to C—P coupling];³¹P NMR (162 MHz, CDCl₃, δ): 37.5; Anal. calcd. for C₃₅H₄₄O₂ClPPd: C,62.78; H, 6.62. Found C, 62.66; H, 6.54.

Single crystals for X-ray analysis of Pd(π-cinnamyl)(SPhos)Cl areobtained by slow cooling of a 1:1 THE/pentane solution in the freezer.

Pd(π-allyl)(RuPhos)Cl

Following the representative procedure: [(allyl)PdCl]₂ (503 mg, 1.43mmol); RuPhos (1.29 g, 2.77 mmol); THF (2 mL); 1 h. Product obtained asa white solid (1.52 g, 85%); ¹H NMR (400 MHz, C₆D₆, δ): 7.60 (t, J=8.7Hz, 1H), 7.18-7.05 (m, 4H), 6.96-6.86 (m, 1H), 6.92 (d, J=7.7 Hz, 1H),6.32 (d, J=7.5 Hz, 1H), 5.03-4.91 (m, 1H), 4.49 (t, J=7.4 Hz, 1H),4.46-4.30 (m, 1H), 4.22-4.08 (m, 1H), 3.37-3.22 (m, 1H), 3.01 (dd, J=9.7Hz, 13.4 Hz, 1H), 2.55-2.04 (m, 5H), 2.03-0.80 (m, 30H); ¹³C NMR (100MHz, C₆D₆, δ): 157.2, 156.7, 141.3 (2 peaks), 134.4, 134.3, 132.7,132.6, 132.4, 132.1, 128.7 (2 peaks), 128.3, 127.9, 125.4, 125.3, 122.5,122.4, 115.3 (2 peaks), 106.4, 105.5, 80.1, 79.8, 70.2, 69.9, 55.8,36.2, 36.0, 35.5, 35.3, 29.5, 29.4, 27.1, 27.0, 26.2, 25.5, 22.3, 22.2,21.6, 21.3 [Observed complexity due to C—P coupling]; ³¹P NMR (162 MHz,C₆D₆, δ): 34.6; Anal. calcd. for C₃₃H₄₈O₂ClPPd: C, 61.02; H, 7.45. FoundC, 60.87; H, 7.42.

Single crystals of Pd(π-allyl)(RuPhos)Cl for X-ray analysis are obtainedby slow cooling of a 1:1 THF/hexanes solution in the freezer.

Pd(π-crotyl)(RuPhos)Cl

Following the representative procedure: [(crotyl)PdCl]₂ (1.022 g, 5.09mmol); RuPhos (2.37 g, 10.18 mmol); THF (2.5 mL); 2 h. Product obtainedas a pale yellow solid (2.93 g, 87%); ¹H NMR (400 MHz, C₆D₆, δ): 7.64(t, J=8.4 Hz, 1H), 7.24-7.09 (m, 3H), 7.06-7.00 (m, 1H), 6.50 (d, J=7.9Hz, 1H), 6.34 (d, J=7.6 Hz, 1H), 4.90-4.80 (m, 1H), 4.58-4.45 (m, 1H),4.31-4.18 (m, 1H), 3.82-3.70 (m, 1H), 3.34-3.26 (m, 1H), 2.57-0.80 (m,38H); ¹³C NMR (100 MHz, C₆D₆, δ): 157.4, 156.9, 142.3, 142.2, 133.9,133.8, 132.8 (2 peaks), 132.5, 128.9 (2 peaks), 128.2, 125.6, 125.5,122.7 (2 peaks), 114.7 (2 peaks), 106.3, 105.4, 99.4, 99.1, 70.2, 70.0,50.7, 37.5, 37.3, 36.7, 36.5, 30.0, 29.2, 27.4, 27.3, 27.1, 26.4, 22.5,22.4, 21.6, 21.4, 17.4 (2 peaks) [Observed complexity due to C—Pcoupling]; ³¹P NMR (162 MHz, C₆D₆, δ): 33.2; HRMS-ESI m/z: [M-Cl],calcd. for C₃₃H₄₈O₂PPd, 627.2583; found 627.2554.

Single crystals of Pd(π-crotyl)(RuPhos)Cl for X-ray analysis areobtained by by slow cooling of a 1:1 THF/hexanes solution in thefreezer.

Pd(π-cinnamyl)(RuPhos)Cl

Following the representative procedure: [(cinnamyl)PdCl]₂ (1.00 g, 1.93mmol); RuPhos (1.80 g, 3.86 mmol); THF (4 mL); 2 h. Product obtained asa yellow solid (2.13 g, 76%); ¹H NMR (400 MHz, CDCl₃, δ): 7.78-7.68 (m,1H), 7.46 (d, J=7.5 Hz, 1H), 7.35-7.18 (m, 7H), 6.92-6.87 (m, 1H), 6.55(d, J=8.2 Hz, 1H), 5.72-5.58 (m, 1H), 4.91-4.77 (m, 1H), 4.52-4.39 (m,1H), 3.00-2.50 (m, 1H), 2.31-2.19 (m, 2H), 2.05-1.94 (m, 2H), 1.74-1.49(m, 8H), 1.44-0.89 (m, 24H); ¹³C NMR (100 MHz, CDCl₃, δ): 156.9, 140.1,137.1 (2 peaks), 135.1, 132.8, 132.7, 131.8, 131.5, 128.7, 128.4, 127.5(2 peaks), 127.4, 125.2, 125.1, 122.4 (2 peaks), 109.7, 109.6, 106.0,100.3, 100.0, 70.4, 52.6, 35.0, 24.8, 30.0, 29.2. 27.0, 26.9, 26.8,26.0, 22.4, 22.0, 21.8 [Observed complexity due to C—P coupling]; ³¹PNMR (162 MHz, CDCl₃, δ): 44.0; HRMS-ESI m/z: [M−Cl], calcd. forC₃₉H₅₂O₂PPd, 689.2740; found 689.2739.

Pd(π-allyl)(XPhos)Cl

Following the representative procedure: [(allyl)PdCl]₂ (858 mg, 2.36mmol); XPhos (2.56 g, 5.37 mmol); THF (5 mL); 3 h. Product obtained as ayellow solid (3.11 g, 97%), product contains ˜5 mol % of THF; ¹H NMR(400 MHz, CDCl₃, δ): 7.98-7.84 (m, 1H), 7.40-7.27 (m, 2H), 7.07-6.99 (m,3H), 5.47-5.26 (m, 1H), 4.54 (t, J=7.1 Hz, 1H), 3.51 (dd, J=9.3 Hz, 13.6Hz, 1H), 3.12-3.01 (m, 1H), 3.00-2.88 (m, 1H), 2.70-2.42 (m, 2H),2.41-2.10 (m, 3H), 1.92-0.73 (m, 38H); ¹³C NMR (100 MHz, CDCl₃, δ):148.7, 146.2, 142.1, 136.6, 136.4, 136.3, 133.7, 133.6, 131.8, 131.6,128.0 (2 peaks), 125.5, 125.4, 120.7, 116.0, 116.0, 79.3, 79.0, 55.7,34.4, 34.1, 33.9, 31.3, 30.4, 29.0, 27.1, 27.0, 26.8, 26.7, 25.6, 25.4,23.9, 22.3 [Observed complexity due to C—P coupling], peaks attributableto THF were observed at 67.7, 25.8; ³¹P NMR (162 MHz, CDCl₃, δ): 48.0;Anal. calcd. for C₃₆H₅₄ClPPd: C, 65.55; H, 8.25. Found C, 65.79; H,8.01.

Pd (π-crotyl) (XPhos)Cl

Following the representative procedure: [(crotyl)PdCl]₂ (1.00 g, 2.54mmol); XPhos (2.42 g, 5.08 mmol); toluene (30 mL); 2 h. Product obtainedas a white solid (3.11 g, 91%); ¹H NMR (400 MHz, CDCl₃, δ): 7.99-7.86(m, 1H), 7.38-7.29 (m, 2H), 7.18-6.99 (m, 3H), 5.19-5.03 (m, 1H),4.32-4.13 (m, 1H), 3.00-2.80 (m, 2H), 2.71-2.42 (m, 2H), 2.31-2.02 (m,3H), 1.95-0.74 (m, 47H); ¹³C NMR (100 MHz, CDCl₃, δ): 148.7, 146.3,142.1, 136.9, 136.7, 136.5, 133.7, 133.6, 132.3, 132.0, 128.8, 128.0 (2peaks), 125.5, 125.4, 120.8, 115.0 (2 peaks), 98.5, 98.2, 50.9, 34.8,34.2, 31.4, 30.5 (2 peaks), 29.2, 27.2, 27.1, 27.0, 26.9, 26.8, 25.8,25.7, 24.0, 22.4, 17.2, 17.1 [Observed complexity due to C—P coupling];³¹P NMR (162 MHz, CDCl₃, δ): 50.8; HRMS-ESI m/z: [M−Cl], calcd. forC₃₇H₅₆PPd, 637.3154; found 637.3153.

Pd(π-cinnamyl)(XPhos)Cl

Following the representative procedure: [(cinnamyl)PdCl]₂ (1.00 g, 1.93mmol); XPhos (1.84 g, 3.86 mmol); toluene (5 mL); 2 h. Product obtainedas a yellow solid (2.27 g, 80%), product contains trace residualtoluene; ¹H NMR (400 MHz, CDCl₃, δ): 8.10-7.95 (m, 1H), 7.52 (d, J=7.5Hz, 2H), 7.42-7.23 (m, 5H), 7.11-7.01 (m, 3H), 5.87-5.69 (m, 1H),5.20-5.06 (m, 1H), 3.08-2.90 (m, 2H), 2.73-0.70 (m, 49H), peaksattributable to toluene were observed at 7.17 and 2.36; ¹³C NMR (100MHz, CDCl₃, δ): 148.9, 146.4, 142.1, 137.2, 136.9, 136.8, 136.7, 136.6,133.8, 133.7, 132.4, 132.2, 129.0, 128.6, 128.4, 128.1, 127.6 (2 peaks),125.7, 125.6, 125.2, 121.0, 109.7, 109.6, 99.4, 99.1, 51.9, 34.5, 34.3,31.7, 30.6, 29.2, 27.3, 27.2, 27.0, 26.9, 26.0, 25.7, 24.1, 22.5[Observed complexity due to C—P coupling], peaks attributable to toluenewere observed at 137.7, 21.4; ³¹P NMR (162 MHz, CDCl₃, δ): 54.3; Anal.calcd. for C₃₆H₅₄ClPPd: C, 68.56; H, 7.95. Found C, 68.85; H, 7.93.

Pd(π-allyl) (BrettPhos)Cl

Following the representative procedure: [(allyl)PdCl]₂ (502 mg, 1.38mmol); BrettPhos (1.48 g, 2.76 mmol); toluene (6 mL); 1 h. Productobtained as an off-white solid (1.95 g, 99%); ¹H NMR (400 MHz, CDCl₃,δ): complex spectrum (see FIG. 1 ); ³¹P NMR (162 MHz, CDCl₃, δ): 54.1,48.7; Anal. calcd. for C₃₈H₅₈O₂ClPPd: C, 63.42; H, 8.12. Found C, 63.17;H, 8.16.

Pd (π-crotyl)(BrettPhos)Cl

Following the representative procedure: [(crotyl)PdCl]₂ (303 mg, 0.769mmol); BrettPhos (827 mg, 1.53 mmol); toluene (2 mL); 1 h. Productobtained as an off-white solid (1.04 g, 92%); ¹H NMR (400 MHz, CDCl₃,δ): complex spectrum (see FIG. 2 ); ³¹P NMR (162 MHz, CDCl₃, δ): 41.4;Anal. calcd. for C₃₉H₆₀O₂ClPPd: C, 63.84; H, 8.24. Found C, 65.01; H,8.57

Pd (π-cinnamyl)(BrettPhos)Cl

Following the representative procedure: [(cinnamyl)PdCl]₂ (503 mg, 0.971mmol); BrettPhos (1.04 g, 1.94 mmol); toluene (4 mL); 0.5 h. Productobtained as a yellow solid (1.34 g, 87%); ¹H NMR (400 MHz, CDCl₃, δ):complex spectrum (see FIG. 3 ); ³¹P NMR (162 MHz, CDCl₃, δ): 43.9; Anal.calcd. for C₄₄H₆₂O₂ClPPd: C, 6.41; H, 7.85. Found C, 66.44; H, 8.15.

Pd (π-allyl)(JackiePhos)Cl

Following the representative procedure: [(allyl)PdCl]₂ (183 mg, 0.500mmol); JackiePhos (797 mg, 1.00 mmol); toluene (5 mL); 1 h. Productobtained as a white solid (529 mg, 54%); ¹H NMR (400 MHz, CDCl₃, δ):complex spectrum (see FIG. 4 ); ³¹P NMR (162 MHz, CDCl₃, δ): 18.1; Anal.calcd. for C₄₂H₄₂F₁₂O₂ClPPd: C, 51.50; H, 4.32. Found C, 51.52; H, 4.15.

Pd(π-allyl)(CyBippyPhos)Cl

Following the representative procedure: [(allyl)PdCl]₂ (245 mg, 0.671mmol); CyBippyPhos (750 mg, 1.34 mmol); THF (4.5 mL); 0.5 h. Productobtained as a pale yellow solid (220 mg, 22%).

Pd(π-allyl)(CyBippyPhos)Cl may also be prepared by the followingprocedure:

A dry 20 mL scintillation vial is charged with 245 mg (0.67 mmol) of[(allyl)PdCl]₂ and transferred into a nitrogen-filled glove box. Thevial is then charged with 750 mg (1.34 mmol) of CyBippyPhos. 4 mL oftoluene is added and the mixture is stirred at rt for 30 minutes. Duringthe stir time, the mixture becomes thick and stirring is difficult. Anadditional 4 mL of toluene is added to allow stirring to continue. Theproduct is fully precipitated by the addition of 8 mL of hexanes. Thesolid is collected by vacuum filtration in air and washed with 3×10 mLof hexanes. The solid is dried in vacuo to give 913 mg (1.23 mmol, 92%)of the title compound as an off-white solid. The product contains <2 wt% of residual toluene.

¹H NMR (400 MHz, CDCl₃, δ): 7.99 (s, 1H), 7.44-7.18 (m, 15H), 6.68-6.55(m, 1H), 5.30-4.99 (m, 1H), 4.60-4.50 (m, 1H), 3.54-3.33 (m, 1H),2.88-2.78 (m, 1H), 2.20-0.77 (m, 22H), 0.48-0.30 (m, 1H); ³¹P NMR (162MHz, CDCl₃, δ): 25.2, 23.2; HRMS-ESI m/z: [M-Cl], calcd. for C₃₇H₅₆PPd,637.3154; found 637.3153. Anal. calcd. for C₃₉H₄₄N₄ClPPd: C, 63.16; H,5.98; N, 7.55. Found C, 63.22; H, 6.14; N, 7.30.

(π-crotyl)Pd(CyBippyPhos)Cl

A dry Schlenk flask is charged with 264 mg (0.67 mmol) of[(crotyl)PdCl]₂ and transferred into a nitrogen-filled glove box. Theflask is then charged with 750 mg (1.34 mmol) of CyBippyPhos. 8 mL oftoluene is added and the mixture is stirred at rt for 1 hour. Theproduct is precipitated by the addition of 20 mL of pentane with coolingin an ice bath. The solid is collected by vacuum filtration in air,washed with 3×10 mL of hexanes, and dried in vacuo to give 904 mg (1.10mmol, 83%) of the title compound as an off-white solid. The product is a⅔ toluene adduct, which is broken by the dissolution in CH₂Cl₂ andevaporating the solvent under reduced pressure at 60° C.

¹H NMR (400 MHz, CDCl₃, δ): complex spectrum (see FIG. 5 ).

¹³C NMR (101 MHz, CDCl₃, δ): 147.2, 142.2, 142.0, 140.5, 140.4, 140.0,139.9, 137.9, 137.6, 137.3, 137.1, 131.4, 131.3, 130.4, 129.1 (2 peaks),129.0, 128.7, 128.6 (2 peaks), 128.5, 128.2 (2 peaks), 127.6, 127.5,126.2 (2 peaks), 126.1, 125.3, 120.1, 119.8, 116.9, 116.8, 116.4, 116.3,115.8 (2 peaks), 115.3 (2 peaks), 100.9, 100.6, 100.4, 52.0, 50.6, 34.9,34.7, 34.4, 34.1, 30.6, 29.9 (2 peaks), 29.6, 29.5, 28.5, 28.3, 27.9,27.7, 27.2, 27.0, 26.9, 26.8, 26.7, 26.6, 26.0, 25.8, 22.4, 21.5[Observed complexity due to C—P coupling].

³¹P NMR (162 MHz, CDCl₃, δ): 22.6 (br), 19.8 (br).

HRMS (ESI) m/z [M−Cl]⁺ Calcd. for C₄₀H₄₆NPPd: 719.2495; Found: 719.2510.

Example 2 (Comparative) Arylation of Acetophenone with 4-Chloroanisole

catalyst X solvent T C time (h) diarylated:mono:acetophenone^(a) remarks1 mol %

Br Br Cl Cl Cl toluene (0.25M) toluene (0.25M) toluene (0.25M) toluene(0.25M) toluene (0.25M) 40 40 60 60 60 18 18 18 18 18 11%:81%:7% 1%:65%:33%  0%:37%:63%  0%:46%:54%  0%:36%:64% 1.2:1.0acetophenone:aryl chloride, isolated yield 60% 1.2:1.0 acetophenone:arylchloride 2.5 eq KOt-Bu 1 mol %

Cl toluene (0.25M) 40 18 39%:37%:61% ^(a)NMR ratios

Representative Procedure: A dry Schlenk tube equipped with ateflon-coated magnetic stir bar is charged with 1 mol % (0.01 mmol) ofPd-precatalyst and 2.00 mmol (2.0 equiv) of t-BuOK. The tube is fittedwith a rubber septum and is evacuated and backfilled with nitrogen. Thisevacuation/backfill procedure is repeated two additional times.4-Chloroanisole (1.00 mmol, 1 equiv) and acetophenone (1.20 mmol, 1.2equiv) are added via syringe followed by 4 mL of anhydrous toluene. Thetube is placed in a preheated (40-60° C.) oil bath and the mixture isstirred vigorously for 18 h. The tube is then removed from the oil bathand the contents are allowed to cool to room temperature. A sample ofthe crude reaction mixture is analysed by ¹H NMR.

Example 3 (According to the Invention) Arylation of Acetophenone with4-Chloroanisole

Representative Procedure: A dry Schlenk tube equipped with ateflon-coated magnetic stir bar is charged with 6.5 mg (0.01 mmol) of(R-allyl)Pd(XPhos)Cl and 224 mg (2.00 mmol) of t-BuOK. The tube isfitted with a rubber septum and is evacuated and backfilled withnitrogen. This evacuation/backfill procedure is repeated two additionaltimes. 4-Chloroanisole (129 μL, 1.05 mmol) and acetophenone (117 μL,1.00 mmol) are added via syringe followed by 4 mL of anhydrous toluene.The tube is placed in a preheated (60° C.) oil bath and the mixture isstirred vigorously for 4 h. The tube is then removed from the oil bathand the contents are allowed to cool to room temperature. A sample isanalysed by GC.

A common problem observed in the α-arylation of methyl ketones is theformation of diarylated products. The results of this Example indicatethat significantly higher yields and higher selectivity (>20:1) formonoarylation:diarylation of acetophenone with chloroarenes are achievedusing (R-allyl)Pd(XPhos)Cl complexes relative to (R-allyl)Pd(AmPhos)Clcomplexes (see Example 2). It is important to note that it is theidentity of the ligand which determines the catalyst's activity.

Example 4 (According to the Invention) Amination of 4-Chloroanisole withMorpholine^([a])

Catalyst GC Conversion^([b]) **1st gen RuPhos PC 66% **2nd gen RuPhos PC 4% **3rd Gen RuPhos PC  5% (allyl)Pd(RuPhos)Cl 80% (crotyl)Pd(RuPhos)Cl87%/97 %^([c])/100%^([c,d]) (cinnamyl)Pd(RuPhos)Cl 95% **1st gen RuPhosPC*  6% (crotyl)Pd(RuPhos)Cl*  5% *with 0.5 mol % added carbazole**comparative PC = palladacycle ^([a])Reaction conditions:4-chloroanisole (1.0 mmol), morpholine (1.2 mmol), NaOtBu (1.2 mmol),catalyst (0.5 mol %), THF (2 mL). ^([b])Determined by GC using dodecaneas an internal standard. ^([c])With 0.5 mol % additional RuPhos added.^([d])Run for 2.5 h.

The above data demonstrate that the (R-π-allyl)Pd(L)Cl (L=RuPhos)complexes of the present invention exhibit better activity than thefirst generation RuPhos palladacycle and significantly better activitythan the second and third generation RuPhos palladacycles.

Moreover, the second and third generation Buchwald palladacycleprecatalysts release an equivalent of genotoxic carbazole uponactivation, unlike the complexes of the present invention. The abovedata also show that the active catalyst generated from(R-π-allyl)Pd(L)Cl complexes does not suffer from inhibition due tocarbazole formation, as do the second and third generationpalladacycles.

Example 5 (According to the Invention) Suzuki-Miyaura Coupling of3-Chloropyridine and p-Tolylboronic Acid^([a])

Precatalyst GC Conversion * 3rd gen XPhos palladacycle 65%(Allyl)Pd(XPhos)Cl 68% (Crotyl)Pd(XPhos)Cl 91%/100%^([b])(Cinnamyl)Pd(XPhos)Cl 90% * comparative. ^([a])Reaction conditions:3-Chloropyridine (1.0 mmol), p-tolylboronic acid (1.5 mmol), K₃PO₄ (2.0mmol), catalyst (2 mol %), THF (2 mL), H₂O (4 mL). ^([b])Run for 2 h.

A dry Schlenk tube, equipped with a Teflon-coated magnetic stir bar andfitted with a rubber septum, is charged with the precatalyst (0.02 mmol,2 mol %) and 204 mg (1.50 mmol, 1.50 equiv) of p-tolylboronic acid. Thetube is evacuated and backfilled with nitrogen. This evacuation/backfillcycle is repeated two additional times. 3-Chloropyridine (95 μL, 1.00mmol, 1.00 equiv) is added followed by 2 mL of anhydrous THF and 4.0 mLof 0.5 M K₃PO₄ (aqueous). The contents are stirred vigorously for 30min. An aliquot is removed and analyzed by gas chromatography.

The (allyl)Pd(XPhos)Cl complex exhibits comparable conversion to the3^(rd) generation XPhos palladacycle. However, both (crotyl)Pd(XPhos)Cland (cinnamyl)Pd(XPhos)Cl promote the Suzuki-Miyaura coupling reactionwith higher rates than the 3^(rd) generation palladacycle.

Example 6 (According to the Invention) Amination of Aryl/HeteroarylChlorides Using (π-Crotyl)Pd(RuPhos)C^([a])

  96%

  95%

  97%

  99%

  98%^([b]) ^([a])Reaction conditions: ArCl/HetArCl (1.0 mmol), amine(1.2 mmol), NaOtBu (1.2 mmol), catalyst (0.5 mol %), RuPhos (0.5 mol %),THF (2 mL). ^([b])1 mol % (π-crotyl)Pd(RuPhos)Cl/1 mol % RuPhos, K₂CO₃,t-AmOH, 110° C., 18 h.

Fast reaction times were observed with 100% conversion reached with1-2.5 h in all cases with the exception of4-(thiophen-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine, which required 18h. The synthesis of4-(thiophen-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine also demonstratescatalyst activation with the use of a weak base (K₂CO₃), compared toNaOt-Bu.

General Procedure for the Amination Reactions

An oven dried Schlenk tube equipped with a Teflon-coated magnetic stirbar is charged with (π-crotyl)Pd(RuPhos)Cl (0.5-1 mol % as indicated),RuPhos (0.5-1 mol % as indicated), aryl chloride (1.00 mmol, if solid),and NaOt-Bu (1.20 mmol). The tube is evacuated and backfilled withnitrogen. This evacuation/backfill cycle is repeated two additionaltimes. Dodecane (GC standard, 0.20 mmol), the amine (1.20 mmol), arylchloride (1.00 mmol, if liquid), and anhydrous THF (2 mL) are addedsequentially via syringe. The tube is placed in a preheated oil bath andstirred for the indicated time. The tube is then removed from the oilbath and allowed to cool to room temperature. The reaction mixture isdiluted with 10 mL of EtOAc and filtered through a pad of Celite. Thesolution is concentrated in vacuo and the residue is chromatographed onsilica gel using a Teledyne ISCO CombiFlashRf.

4-(4-methoxyphenyl)morpholine

According to the general procedure, a mixture of 4-chloroanisole (123μL, 1.00 mmol), morpholine (105 μL, 1.20 mmol), NaOtBu (115 mg, 1.20mmol), (π-crotyl)Pd(RuPhos)Cl (3.3 mg, 0.005 mmol), RuPhos (2.3 mg,0.005 mmol), and 2 mL THF are stirred at 80° C. for 2.5 h. The crudematerial is chromatographed on silica gel with a gradient of 0-20%EtOAc/hexanes as the eluent to give 186 mg (0.96 mmol, 96%) of4-(4-methoxyphenyl)morpholine as a colorless solid. The spectroscopicdata match those previously reported (D. Maiti, B. P. Fors, J. L.Henderson, Y. Nakamura, S. L. Buchwald, Chem. Sci. 2011, 2, 57).

N,N-diethyl-6-methoxypyridin-2-amine

According to the general procedure, a mixture of2-chloro-6-methoxypyridine (119 μL, 1.00 mmol), diethylamine (124 μL,1.20 mmol), NaOtBu (115 mg, 1.20 mmol), (π-crotyl)Pd(RuPhos)Cl (3.3 mg,0.005 mmol), RuPhos (2.3 mg, 0.005 mmol), and 2 mL THF are stirred at80° C. for 70 minutes. The crude material is chromatographed on silicagel with a gradient of 0-5% EtOAc/hexanes as the eluent to give 171 mg(0.95 mmol, 95%) of N,N-diethyl-6-methoxypyridin-2-amine as a colorlessoil.

¹H NMR (400 MHz, CDCl₃, δ): 7.33 (t, J=7.5 Hz, 1H), 5.99 (d, J=7.8 Hz,1H), 5.93 (d, J=7.8 Hz, 1H), 3.86 (s, 3H), 3.49 (q, J=7.0 Hz, 4H), 1.81(t, J=7.0 Hz, 6H).

¹³C NMR (100 MHz, CDCl₃, δ): 163.4, 156.7, 139.8, 96.8, 95.2, 52.9,42.7, 13.2.

HRMS (ESI) m/z [M+H]⁺ Calcd. for C₁₀H₁₇N₂O: 181.1341. Found: 181.1318

1-(pyrazin-2-yl)indoline

According to the general procedure, a mixture of 2-chloropyrazine (89μL, 1.00 mmol), indoline (135 μL, 1.20 mmol), NaOtBu (115 mg, 1.20mmol), (π-crotyl)Pd(RuPhos)Cl (3.3 mg, 0.005 mmol), RuPhos (2.3 mg,0.005 mmol), and 2 mL THF are stirred at 80° C. for 1 hour. The crudematerial is chromatographed on silica gel with a gradient of 0-50%EtOAc/hexanes as the eluent to give 191 mg (0.97 mmol, 97%) of1-(pyrazin-2-yl)indoline as a yellow solid.

¹H NMR (400 MHz, CDCl₃, δ): 8.14-8.28 (m, 3H), 8.00 (app d, J=2.6 Hz,1H), 7.13-7.27 (m, 2H), 6.88-6.93 (m, 1H), 4.05 (t, J=8.7 Hz, 2H), 3.24(t, J=8.7 Hz, 2H).

¹³C NMR (100 MHz, CDCl₃, δ): 151.6, 144.1, 141.8, 134.3, 132.0, 131.3,127.5, 124.8, 121.6, 114.2, 48.7, 27.9.

Anal. Calcd. for C₁₂H₁₁N₃: C, 73.07; H, 5.62; N, 21.30. Found: C, 73.17;H, 5.63; N, 21.42.

N-methyl-N-phenylquinolin-6-amine

According to the general procedure, a mixture of 6-chloroquinoline (164mg, 1.00 mmol), N-methylaniline (130 μL, 1.20 mmol), NaOtBu (115 mg,1.20 mmol), (π-crotyl)Pd(RuPhos)Cl (3.3 mg, 0.005 mmol), RuPhos (2.3 mg,0.005 mmol), and 2 mL THF are stirred at 80° C. for 1 hour. The crudematerial is chromatographed on silica gel with a gradient of 0-50%EtOAc/hexanes as the eluent to give 231 mg (0.99 mmol, 99%) ofN-methyl-N-phenylquinolin-6-amine as a yellow oil. The spectroscopicdata match those previously reported (M. Tobisu, A. Yasutome, K.Yamakawa, T. Shimasaki, N. Chatani, Tetrahedron 2012, 68, 5157).

4-(thiophen-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine

The general procedure is followed with the following modifications: amixture of 3-chlorothiophene (93 μL, 1.00 mmol), benzomorpholine (140μL, 1.20 mmol), K₂CO₃ (194 mg, 1.40 mmol), (π-crotyl)Pd(RuPhos)Cl (6.6mg, 0.01 mmol), RuPhos (4.7 mg, 0.01 mmol), and 2 mL t-AmOH are stirredat 110° C. for 20 hour. The crude material is chromatographed on silicagel with a gradient of 0-5% EtOAc/hexanes as the eluent to give 212 mg(0.98 mmol, 98%) of4-(thiophen-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine as a yellow oil.

¹H NMR (400 MHz, CDCl₃, δ): 7.30 (dd, J=3.2 Hz, 5.2 Hz, 1H), 7.07 (dd,J=1.4 Hz, 5.2 Hz, 1H), 6.92-6.98 (m, 1H), 6.85-6.91 (m, 1H), 6.81 (dd,J=1.4 Hz, 3.2 Hz, 1H), 6.73-6.81 (m, 2H), 4.33 (t, J=4.5 Hz, 2H), 3.69(t, J=4.4 Hz, 2H).

¹³C NMR (100 MHz, CDCl₃, δ): 146.1, 144.5, 133.1, 125.4, 124.1, 121.2,120.1, 117.0, 116.3, 112.3, 64.5, 49.0.

Anal. Calcd. for C₁₂H₁₁NOS: C, 66.33; H, 5.10; N, 6.45. Found: C, 66.42;H, 5.24; N, 6.42.

Example 7 (According to the Invention) Suzuki-Miyaura Reactions Using(π-Crotyl)Pd(XPhos)Cl^([a])

  95% rt, 2 h

  98% 45° C., 1 h

  94% rt, 1 h

  88% rt, 30 min

  92% rt, 2 h

  80%^([b]) 45° C., 5 h ^([a])Reaction conditions: HetArCl (1.0 mmol),ArB(OH)₂ (1.5 mmol), K₃PO₄ (2.0 mmol), catalyst (2 mol %), THF (2 mL),H₂O (4 mL). ^([b])Isolated as the hydromethanesulfonate salt for ease ofpurification.

Using (crotyl)Pd(XPhos)Cl catalyst, a range of heteroaryl chlorides maybe coupled with challenging aryl and heteroaryl boronic acids withuniformly high yields, including those which are prone to rapidprotodeboronation, at or slightly above room temperature (up to 45° C.)due to the fast generation of the active “L-Pd(0)”. For example,2-thienylboronic acid, 2-furanboronic acid, and2,6-difluorophenylboronic acid were all coupled in high yield with shortreaction times (≤1 hour).

General Procedure for the Suki-Miyaura Couplings

An oven dried Schlenk tube equipped with a Teflon-coated magnetic stirbar is charged with (π-crotyl)Pd(XPhos)Cl (2 mol %), heteroaryl chloride(1.00 mmol, if solid), and aryl/heteroarylboronic acid (1.5 mmol). Thetube is evacuated and backfilled with nitrogen. This evacuation/backfillcycle is repeated two additional times. The heteroaryl chloride (1.00mmol, if liquid), anhydrous THF (2 mL), and aqueous 0.5 M K₃PO₄ (4.0 mL)are added sequentially via syringe. The tube is stirred at roomtemperature or placed in a preheated oil bath at 45° C. as indicated andstirred for the indicated time. If heated, the tube is then removed fromthe oil bath and allowed to cool to room temperature. The reactionmixture is diluted with 10 mL of EtOAc and 10 mL of H₂O, and then theaqueous phase is extracted with 3×10 mL of EtOAc. The combined organicextracts are dried over anhydrous MgSO₄, filtered, and concentrated invacuo. The residue is chromatographed on silica gel using a TeledyneISCO CombiFlashRf, unless otherwise noted.

3-(4-tolyl)pyridine

According to the general procedure, a mixture of 3-chloropyridine (95μL, 1.00 mmol), p-tolylboronic acid (204 mg, 1.50 mmol),(π-crotyl)Pd(XPhos)Cl (14 mg, 0.02 mmol), 2 mL THF, and 4 mL of 0.5 Maqueous K₃PO₄ are stirred at room temperature for 2 hours. The crudematerial is chromatographed on silica gel with a gradient of 10-40%EtOAc/hexanes as the eluent to give 160 mg (0.95 mmol, 95%) of3-(4-tolyl)pyridine as a colorless solid. The spectroscopic data matchthose previously reported (C. L. Cioffi, W. T. Spencer, J. J. Richards,R. J. Herr, J. Org. Chem. 2004, 69, 2210).

2-(thiophen-2-yl)quinoline

According to the general procedure, a mixture of 2-chloroquinoline (164mg, 1.00 mmol), 2-thienylboronic acid (192 mg, 1.50 mmol),(π-crotyl)Pd(XPhos)Cl (14 mg, 0.02 mmol), 2 mL THF, and 4 mL of 0.5 Maqueous K₃PO₄ are stirred at 45° C. for 2 hours. The crude material ischromatographed on silica gel with a gradient of 0-5% EtOAc/hexanes asthe eluent to give 208 mg (0.99 mmol, 99%) of 2-(thiophen-2-yl)quinolineas a colorless solid. The spectroscopic data match those previouslyreported (F.-F. Zhuo, W.-W. Xie, Y.-X. Yang, L. Zhang, P. Wang, R. Yuan,C.-S. Da, J. Org. Chem. 2013, 78, 3243).

4-(furan-2-yl)-2, 6-dimethoxypyrimidine

According to the general procedure, a mixture of6-chloro-2,4-dimethoxypyrimidine (175 mg, 1.00 mmol), 2-furanboronicacid (168 mg, 1.50 mmol), (π-crotyl)Pd(XPhos)Cl (14 mg, 0.02 mmol), 2 mLTHF, and 4 mL of 0.5 M aqueous K₃PO₄ are stirred at room temperature for1 hour. The crude material is chromatographed on silica gel with agradient of 0-10% EtOAc/hexanes as the eluent to give 194 mg (0.94 mmol,94%) of 4-(furan-2-yl)-2,6-dimethoxypyrimidine as a colorless solid. ¹HNMR (400 MHz, CDCl₃, δ): 7.53 (dd, J=0.9 Hz, 1.9 Hz, 1H), 7.19 (dd,J=0.7 Hz, 3.5 Hz, 1H), 6.69 (s, 1H), 6.53 (dd, J=1.7 Hz, 3.4 Hz, 1H)4.02 (s, 3H), 3.99 (s, 3H).

¹³C NMR (100 MHz, CDCl₃, δ): 172.6, 165.6, 157.4, 152.2, 144.6, 112.3,111.9, 95.0, 54.8, 54.0. Anal. Calcd. for C₁₀H₁₀N₂O₃: C, 58.25; H, 4.89;N, 13.59. Found: C, 58.19; H, 4.72; N, 13.42.

2-(2,6-difluorophenyl)-6-methoxypyridine

According to the general procedure, a mixture of2-chloro-6-methoxypyridine (119 μL, 1.00 mmol),2,6-difluorophenylboronic acid (237 mg, 1.50 mmol),(π-crotyl)Pd(XPhos)Cl (14 mg, 0.02 mmol), 2 mL THF, and 4 mL of 0.5 Maqueous K₃PO₄ are stirred at room temperature for 30 minutes. The crudematerial is chromatographed on silica gel with a gradient of 0-5%EtOAc/hexanes as the eluent to give 195 mg (0.88 mmol, 88%) of2-(2,6-difluorophenyl)-6-methoxypyridine as a pale yellow oil.

¹H NMR (400 MHz, CDCl₃, δ): 7.64 (t, J=7.8 Hz, 1H), 7.35-7.26 (m, 1H),7.05 (d, J=7.1 Hz, 1H), 7.00-6.92 (m, 2H), 6.75 (d, J=8.3 Hz, 1H), 3.95(s, 3H).

¹³C NMR (100 MHz, CDCl₃, δ): 163.8, 160.5 (dd, J=250.7 Hz, 6.97 Hz),146.7, 138.6, 129.8 (t, J=10.23 Hz), 118.8 (t, J=1.95 Hz), 118.2 (t,J=17.23 Hz), 111.8 (dd, J=26.1 Hz, 6.6 Hz), 110.3, 53.6. Anal. Calcd.for C₁₂H₉F₂NO: C, 65.16; H, 4.10; N, 6.33. Found: C, 65.14; H, 4.37; N,6.46.

5-(dibenzo[b,d]furan-4-yl)-1,3-dimethyl-1H-pyrazole

According to the general procedure, a mixture of5-chloro-1,3-dimethyl-1H-pyrazole (115 μL, 1.00 mmol),dibenzo[b]-furan-4-boronic acid (318 mg, 1.50 mmol),(π-crotyl)Pd(XPhos)Cl (14 mg, 0.02 mmol), 2 mL THF, and 4 mL of 0.5 Maqueous K₃PO₄ are stirred at room temperature for 2 hours. The crudematerial is chromatographed on silica gel with a gradient of 0-10%EtOAc/hexanes as the eluent to give 240 mg (0.92 mmol, 92%) of5-(dibenzo[b,d]furan-4-yl)-1,3-dimethyl-1H-pyrazole as an off-whitesolid.

¹H NMR (400 MHz, CDCl₃, δ): 8.02-7.97 (m, 2H), 7.57 (d, J=8.8 Hz, 1H),7.58-7.36 (m, 4H), 6.33 (s, 1H), 3.85 (s, 3H), 2.39 (s, 3H).

¹³C NMR (100 MHz, CDCl₃, δ): 156.2, 153.3, 147.9, 139.1, 128.0, 127.7,125.0, 124.0, 123.2, 123.0, 121.1, 120.9, 115.6, 112.0, 107.1, 37.4,13.7.

Anal. Calcd. for C₁₇H₁₄N₂O: C, 77.84; H, 5.38; N, 10.68. Found: C,77.93; H, 5.29; N, 10.56.

5-methyl-6-(thiophen-3-yl)imidazo[1,2-a]pyridine hydromethanesulfonate

According to the general procedure, a mixture of6-bromo-5-methylimidazo[1,2,a]pyridine (167 mg, 1.00 mmol),3-thienylboronic acid (152 mg, 1.50 mmol), (π-crotyl)Pd(XPhos)Cl (14 mg,0.02 mmol), 2 mL THF, and 4 mL of 0.5 M aqueous K₃PO₄ are stirred at 45°C. for 5 hours. The crude material is taken up in 10 mL of isopropylacetate and stirred. 0.08 mL of methanesulfonic acid is added slowly asa precipitate developed, and the mixture is stirred at rt for 30minutes. The solid is collected by vacuum filtration, washed (3×5 mLisopropyl acetate, 1×10 mL hexanes), and dried in vacuo to give 194 mg(0.80 mmol, 80%) of 5-methyl-6-(thiophen-3-yl)imidazo[1,2-a]pyridinehydromethanesulfonate as a tan solid.

¹H NMR (400 MHz, 4:1 D₂O/DMSO-d₆, δ): 8.18 (s, 1H), 8.06 (s, 1H), 7.97(d, J=9.3 Hz, 1H), 7.85 (d, J=9.3 Hz, 1H), 7.70-7.60 (m, 2H), 7.32 (d,J=4.6 Hz, 1H), 2.87-2.77 (m, 6H).

¹³C NMR (100 MHz, 4:1 D₂O/DMSO-d₆, δ): 140.4, 137.8, 137.3, 137.2,130.1, 128.5, 127.3, 126.5, 123.9, 114.7, 110.4, 40.1, 17.4.

HRMS (ESI) m/z [M+H−OMs]⁺ Calcd. for C₁₂H₁₀N₂S: 215.0643. Found:215.0644.

Example 8 (According to the Invention) Monoarylation of Ketone Enolates

The XPhos complexes (π-allyl)Pd(XPhos)Cl, (π-crotyl)Pd(XPhos)Cl and(π-cinnamyl)Pd(XPhos)Cl were evaluated in the monoarylation of ketoneenolates. These complexes all promoted rapid conversion (≥95%) after 1hour in the α-arylation of acetophenone with 4-chloroanisole (see FIG. 6.). The rate of conversion is significantly lower when G3 XPhos wasemployed as the precatalyst; 34% conversion is observed at 1 hour, and 4hours was necessary to reach high conversion (93%). Carbazole is shownto retard the rate of this reaction, albeit to a lesser extent than inamination. The kinetic profile of the reaction catalyzed by(π-allyl)Pd(XPhos)Cl with 1 mol % of carbazole added nearly matched thatof the G3 XPhos-catalyzed reaction.

Four examples of ketone enolate arylations using (π-allyl)Pd(XPhos)Clhighlight the versatility of this catalyst:

General Procedure for the Ketone Enolate Arylation Reactions

An oven dried Schlenk tube equipped with a Teflon-coated magnetic stirbar is charged with (π-allyl)Pd(XPhos)Cl (1-2 mol %, as indicated), arylchloride (1.00 mmol, if solid), and KOt-Bu (2.00-2.40 mmol, asindicated). The tube is capped with a rubber septum and was evacuatedand backfilled with nitrogen. This evacuation/backfill cycle is repeatedtwo additional times. Dodecane (GC standard, 0.20 mmol), the ketone(1.20 mmol), aryl chloride (1.00 mmol, if liquid), and anhydrous toluene(4 mL) are added sequentially via syringe. The tube is placed in apreheated oil bath (60° C.) and stirred for the indicated time. The tubeis then removed from the oil bath and allowed to cool to roomtemperature. Saturated NH₄Cl (4 mL) and EtOAc (10 mL) are added, and theaqueous phase is extracted with EtOAc (3×10 mL). The organic extractsare combined, dried over anhydrous MgSO₄, filtered, and concentrated invacuo. The residue is chromatographed on silica gel using a TeledyneISCO CombiFlashRf.

2-(4-methoxyphenyl)-1-phenylethan-1-one

According to the general procedure, a mixture of 4-chloroanisole (123μL, 1.00 mmol), acetophenone (140 μL, 1.20 mmol), KOtBu (224 mg, 2.00mmol), (π-allyl)Pd(XPhos)Cl (6.6 mg, 0.01 mmol), and 4 mL of toluene arestirred at 60° C. for 2 hours. The crude material is chromatographed onsilica gel with a gradient of 0-4% EtOAc/hexanes as the eluent to give210 mg (0.93 mmol, 93%) of 2-(4-methoxyphenyl)-1-phenylethan-1-one as acolorless solid. The spectroscopic data match those previously reported(M. R. Biscoe, S. L. Buchwald, Org. Lett. 2009, 11, 1773).

1-(pyridin-3-yl)-2-(quinolin-6-yl)ethan-1-one

According to the general procedure, a mixture of 6-chloroquinoline (164mg, 1.00 mmol), 3-acetylpyridine (132 μL, 1.20 mmol), KOtBu (269 mg,2.40 mmol), (π-allyl)Pd(XPhos)Cl (6.6 mg, 0.01 mmol), and 4 mL oftoluene are stirred at 60° C. for 4 hours. The crude material ischromatographed on silica gel with EtOAc as the eluent to give 236 mg(0.95 mmol, 95%) of 1-(pyridin-3-yl)-2-(quinolin-6-yl)ethan-1-one as apale yellow solid.

¹H NMR (400 MHz, CDCl₃, δ): 9.29 (s, 1H), 8.90 (d, J=3.5 Hz, 1H), 8.88(d, J=3.5 Hz, 1H), 8.29 (d, J=8.2 Hz, 1H), 8.17-8.02 (m, 2H), 7.72 (s,1H), 7.65 (d, J=8.5 Hz, 1H), 7.47-7.31 (m, 2H), 4.50 (s, 2H).

¹³C NMR (100 MHz, CDCl₃, δ): 196.1, 153.8, 150.6, 150.1, 147.6, 135.9,135.8, 132.1, 131.8, 131.2, 130.1, 128.4, 128.2, 123.9, 121.5, 45.7.

HRMS (ESI) m/z [M+H]⁺ Calcd. for C₁₆H₁₃N₂O: 249.1028. Found: 249.1020.

1-(furan-2-yl)-2-(4-(trifluoromethyl)phenyl)ethan-1-one

According to the general procedure, a mixture of4-chlorobenzotrifluoride (133 μL, 1.00 mmol), 2 acetylfuran (132 μL,1.20 mmol), KOtBu (269 mg, 2.40 mmol), (π-allyl)Pd(XPhos)Cl (13.2 mg,0.02 mmol), and 4 mL of toluene are stirred at 60° C. for 4 hours. Thecrude material is chromatographed on silica gel with EtOAc as the eluentto give 236 mg (0.95 mmol, 95%) of1-(furan-2-yl)-2-(4-(trifluoromethyl)phenyl)ethan-1-one as a pale yellowsolid. The spectroscopic data match those previously reported (T. Miura,S. Fujioka, N. Takemura, H. Iwasaki, M. Ozeki, N. Kojima, M. Yamashita,Synthesis, 2014, 46, 496).

1-(naphthalen-1-yl)-2-(pyridin-3-yl)ethan-1-one

According to the general procedure, a mixture of 3-chloropyridine (95μL, 1.00 mmol), 1-acetonaphthalene (182 μL, 1.20 mmol), KOtBu (269 mg,2.40 mmol), (π-allyl)Pd(XPhos)Cl (13.2 mg, 0.02 mmol), and 4 mL oftoluene are stirred at 60° C. for 4 hours. The crude material ischromatographed on silica gel with 50% EtOAc/hexanes as the eluent togive 237 mg (0.96 mmol, 96%) of1-(naphthalen-1-yl)-2-(pyridin-3-yl)ethan-1-one as a yellow oil.

1H NMR (400 MHz, CDCl₃, δ): 8.61-8.49 (m, 3H), 8.01-7.94 (m, 2H), 7.89(dd, J=1.6 Hz, 7.9 Hz, 1H), 7.63 (dt, J=1.8 Hz, 7.8 Hz, 1H), 7.60-7.48(m, 3H), 7.29-7.23 (m, 1H), 4.38 (s, 2H).

¹³C NMR (100 MHz, CDCl₃, δ): 200.3, 150.8, 148.5, 137.2, 135.0, 134.1,133.4, 130.4 (2 peaks), 128.6, 128.3, 128.2, 126.8, 125.8, 124.4, 123.6,45.7.

HRMS (ESI) m/z [M+1-1]⁺ Calcd. for C₁₇H₁₄NO: 248.1075. Found: 248.1075.

Example 9 (According to the Invention) Trifluoromethanation Using(π-allyl)Pd(BrettPhos)Cl

In a nitrogen filled glovebox a 2 dram reaction vial equipped with aTeflon-coated magnetic stir bar is charged with (allyl)Pd(BrettPhos)Cl(21.6 mg, 30 μmol), BrettPhos (16.1 mg, 30 μmol), and potassium fluoride(58.1 mg, 1.0 mmol). Dioxane (1.65 mL), triethyl(trifluoromethyl)silane(188 μL, 1.0 mmol), and 1-nbutyl-4-chlorobenzene (84.3 μL, 0.50 mmol)are added via syringe. The reaction vial is capped with an open top capand PTFE Faced Silicone septum, removed from the glovebox, and placed ona preheated aluminum block (120° C.) and stirred vigorously for 16hours. After cooling to room temperature the vial is opened to air andan aliquot (˜200 μL) is removed, passed through a plug of Celite, elutedwith ethyl acetate (2 mL) and analyzed by GC. The benzotrifluorideproduct is observed in 84% GC yield (uncalibrated).

This experiment demonstrates that the precatalyst(π-allyl)Pd(BrettPhos)Cl is competent in the trifluoromethanation of4-n-butyl-1-chlorobenzene.

Further aspects and embodiments of the present disclosure are set out inthe following numbered clauses:

-   1. A palladium(II) complex of formula (1):

-   -   wherein:    -   R₁ and R₂ are independently organic groups having 1-20 carbon        atoms, or R₁ and R₂ are linked to form a ring structure with E;    -   R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are independently —H or        organic groups having 1-20 carbon atoms; or    -   R₁/R₃ or R₂/R₃ forms a ring structure with the atoms to which        they are attached and in this instance R₄/R₅, R₅/R₆, R₇/R₈,        R₈/R₉, R₉/R₁₀ or R₁₀/R₁₁ may independently form a ring structure        with the carbon atoms to which they are attached or R₁, R₂, R₄,        R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are as defined above;    -   R₁₂ is an organic group having 1-20 carbon atoms;    -   m is 0, 1, 2, 3, 4 or 5;    -   E is P or As; and    -   X is a coordinating anionic ligand;        provided that the palladium complex of formula (1) is not        (π-crotyl)PdCl(dicyclohexylphosphino-2-biphenyl).

-   2. A palladium(II) complex according to clause 1, wherein E is P.

-   3. A palladium(II) complex according to clause 2, wherein R₁ and R₂    are more sterically bulky than a cyclohexyl group when R₇, R₈, R₉,    R₁₀ and/or R₁₁ are less sterically bulky than a cyclohexyl group.

-   4. A palladium(II) complex according to clause 2, wherein R₁ and R₂    are less sterically bulky than a cyclohexyl group when R₇, R₈, R₉,    R₁₀ and/or R₁₁ are more sterically bulky than a cyclohexyl group.

-   5. A palladium(II) complex according to any one of the preceding    clauses, wherein R₁ and R₂ are independently selected from the group    consisting of substituted and unsubstituted straight-chain alkyl,    substituted and unsubstituted branched-chain alkyl, substituted and    unsubstituted cycloalkyl, substituted and unsubstituted aryl, and    substituted and unsubstituted heteroaryl wherein the heteroatoms are    independently selected from sulfur, nitrogen and oxygen.

-   6. A palladium(II) complex according to any one of the preceding    clauses, wherein R₃, R₄, R₅ and R₆ are independently selected from    the group consisting of —H, substituted and unsubstituted    straight-chain alkyl, substituted and unsubstituted branched-chain    alkyl, substituted and unsubstituted cycloalkyl, substituted and    unsubstituted alkoxy, substituted and unsubstituted aryl,    substituted and unsubstituted heteroaryl, substituted and    unsubstituted —N(alkyl)₂ (wherein the alkyl groups may be the same    or different and are independently selected from straight-chain or    branched-chain groups), substituted and unsubstituted    —N(cycloalkyl)₂ (wherein the cycloalkyl groups may be the same or    different), substituted and unsubstituted —N(aryl)₂ (wherein the    aryl groups may be the same or different), substituted and    unsubstituted —N(heteroaryl)₂ (wherein the heteroaryl groups may be    the same or different) and substituted and unsubstituted    heterocycloalkyl groups.

-   7. A palladium(II) complex according to clause 6, wherein each of    R₃, R₄, R₅ and R₆ are —H.

-   8. A palladium(II) complex according to clause 6, wherein two of R₃,    R₄, R₅ and R₆ are —H, and the other two of R₃, R₄, R₅ and R₆ are    independently selected from the group consisting of unsubstituted    straight-chain alkyl, unsubstituted branched-chain alkyl,    unsubstituted cycloalkyl and unsubstituted alkoxy.

-   9. A palladium(II) complex according to any one of the preceding    clauses, wherein R₇, R₈, R₉, R₁₀ and R₁₁ are independently selected    from the group consisting of —H, substituted and unsubstituted    straight-chain alkyl, substituted and unsubstituted branched-chain    alkyl, substituted and unsubstituted cycloalkyl, substituted and    unsubstituted alkoxy, substituted and unsubstituted aryl,    substituted and unsubstituted heteroaryl, substituted and    unsubstituted —N(alkyl)₂ (wherein the alkyl groups may be the same    or different and are independently selected from straight-chain or    branched-chain groups), substituted and unsubstituted    —N(cycloalkyl)₂ (wherein the cycloalkyl groups may be the same or    different), substituted and unsubstituted —N(aryl)₂ (wherein the    aryl groups may be the same or different), substituted and    unsubstituted —N(heteroaryl)₂ (wherein the heteroaryl groups may be    the same or different) and substituted and unsubstituted    heterocycloalkyl groups.

-   10. A palladium(II) complex according to clause 9, wherein each of    R₇, R₈, R₉, R₁₀ and R₁₁ are —H.

-   11. A palladium(II) complex according to clause 9, wherein three of    R₇, R₈, R₉, R₁₀ and R₁₁ are —H, and the other two of R₇, R₈, R₉, R₁₀    and R₁₁ are independently selected from the group consisting of    unsubstituted straight-chain alkyl, unsubstituted branched-chain    alkyl, unsubstituted cycloalkyl, unsubstituted alkoxy, unsubstituted    —N(alkyl)₂ (wherein the alkyl groups may be the same or different    and may be independently selected from straight-chain or    branched-chain groups) and unsubstituted —N(aryl)₂ (wherein the aryl    groups may be the same or different).

-   12. A palladium(II) complex according to clause 9, wherein two of    R₇, R₈, R₉, R₁₀ and R₁₁ are —H, and the other three of R₇, R₈, R₉,    R₁₀ and R₁₁ are independently selected from the group consisting of    unsubstituted straight-chain alkyl, unsubstituted branched-chain    alkyl, unsubstituted cycloalkyl, unsubstituted alkoxy, unsubstituted    —N(alkyl)₂ (wherein the alkyl groups may be the same or different    and may be independently selected from straight-chain or    branched-chain groups) and unsubstituted —N(aryl)₂ (wherein the aryl    groups may be the same or different).

-   13. A palladium(II) complex according to any one of preceding    clauses, wherein the monodentate tertiary phosphine ligand is    selected from the group consisting of:

-   14. A palladium(II) complex according to any one of the preceding    clauses, wherein R₁₂ is selected from the group consisting of    substituted and unsubstituted straight-chain alkyl, substituted and    unsubstituted branched-chain alkyl, substituted and unsubstituted    cycloalkyl, substituted and unsubstituted aryl, and substituted and    unsubstituted heteroaryl wherein the heteroatoms are independently    selected from sulfur, nitrogen and oxygen.-   15. A palladium(II) complex according to any one of the preceding    clauses, wherein X is a halo group or a trifluoroacetate group.-   16. A palladium(II) complex according to any one of the preceding    clauses, wherein the complex of formula (1) is selected from the    group consisting of:

-   17. A palladium complex of formula (2);

-   -   wherein:    -   R₁₈ and R₁₉ are independently selected from the group consisting        of -Me, -Et, —^(n)Pr, —^(i)Pr, —^(n)Bu, —^(i)Bu, cyclohexyl and        cycloheptyl;    -   R₁₂ is an organic group having 1-20 carbon atoms;    -   R₂₀, R₂₁, R₂₂, R₂₃ and R₂₄ are independently —H or organic        groups having 1-20 carbon atoms; or one or both pairs selected        from R₂₀/R₂₁ or R₂₂/R₂₃ may independently form a ring structure        with the atoms to which they are attached;    -   m is 0, 1, 2, 3, 4 or 5; and    -   X is a coordinating anionic ligand.

-   18. A palladium(II) complex according to clause 17, wherein R₁₈ and    R₁₉ are the same and are cyclohexyl groups.

-   19. A palladium(II) complex according to clause 17 or clause 18,    wherein R₂₀ and R₂₁ are independently selected from the group    consisting of —H, substituted and unsubstituted straight-chain    alkyl, substituted and unsubstituted branched-chain alkyl,    substituted and unsubstituted cycloalkyl, substituted and    unsubstituted alkoxy, substituted and unsubstituted aryl,    substituted and unsubstituted heteroaryl, substituted and    unsubstituted —N(alkyl)₂ (wherein the alkyl groups may be the same    or different and are independently selected from straight-chain or    branched-chain groups), substituted and unsubstituted    —N(cycloalkyl)₂ (wherein the cycloalkyl groups may be the same or    different), substituted and unsubstituted —N(aryl)₂ (wherein the    aryl groups may be the same or different), substituted and    unsubstituted —N(heteroaryl)₂ (wherein the heteroaryl groups may be    the same or different) and substituted and unsubstituted    heterocycloalkyl groups.

-   20. A palladium(II) complex according to clause 19, wherein both of    R₂₀ and R₂₁ are —H.

-   21. A palladium(II) complex according to any one of clauses 17 to    20, wherein R₂₂ and R₂₄ are independently selected from the group    consisting of —H, substituted and unsubstituted straight-chain    alkyl, substituted and unsubstituted branched-chain alkyl,    substituted and unsubstituted cycloalkyl, substituted and    unsubstituted alkoxy, substituted and unsubstituted-thioalkyl,    substituted and unsubstituted aryl, substituted and unsubstituted    heteroaryl, substituted and unsubstituted —N(alkyl)₂ (wherein the    alkyl groups may be the same or different and are independently    selected from straight-chain or branched-chain groups), substituted    and unsubstituted —N(cycloalkyl)₂ (wherein the cycloalkyl groups may    be the same or different), substituted and unsubstituted —N(aryl)₂    (wherein the aryl groups may be the same or different), substituted    and unsubstituted —N(heteroaryl)₂ (wherein the heteroaryl groups may    be the same or different).

-   22. A palladium(II) complex according to any one of clauses 17 to    21, wherein R₂₃ is selected from the group consisting of —H,    substituted and unsubstituted straight-chain alkyl, substituted and    unsubstituted branched-chain alkyl, substituted and unsubstituted    cycloalkyl, substituted and unsubstituted alkoxy, substituted and    unsubstituted aryl, and substituted and unsubstituted heteroaryl.

-   23. A palladium(II) complex according to any one of clauses 17 to    22, wherein each of R₂₂, R₂₃ and R₂₄ are phenyl groups.

-   24. A palladium(II) complex according to any one of clauses 17 to    23, wherein the complex of formula (2) is selected from the group    consisting of:

-   25. A process for the preparation of a complex of formula (1) or a    complex of formula (2), the process comprising the step of reacting    a complex of formula (3) with a monodentate biaryl ligand of    formula (4) or a monodentate bi-heteroaryl tertiary phosphine ligand    of formula (5) to form the complex of formula (1) or the complex of    formula (2),

-   -   wherein,    -   R₁ and R₂ are independently organic groups having 1-20 carbon        atoms, or R₁ and R₂ are linked to form a ring structure with E;    -   R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are independently —H or        organic groups having 1-20 carbon atoms; or    -   one or more pairs selected from R₁/R₃, R₂/R₃, R₃/R₄, R₄/R₅,        R₅/R₆, R₇/R₈, R₈/R₉, R₉/R₁₀ or R₁₀/R₁₁ independently may form a        ring structure with the carbon atoms to which they are attached;    -   R₁₂ is an organic group having 1-20 carbon atoms;    -   R₁₈ and R₁₉ are independently selected from the group consisting        of -Me, -Et, —^(n)Pr, —^(i)Pr, —^(n)Bu, —^(i)Bu, cyclohexyl and        cycloheptyl;    -   R₂₀, R₂₁, R₂₂, R₂₃ and R₂₄ are independently —H or organic        groups having 1-20 carbon atoms; or one or both pairs selected        from R₂₀/R₂₁ or R₂₂/R₂₃ independently may form a ring structure        with the atoms to which they are attached;    -   m is 0, 1, 2, 3, 4 or 5;    -   E is P or As; and    -   X is a coordinating anionic ligand;    -   provided that the palladium complex of formula (1) is not        (π-crotyl)PdCl(dicyclohexylphosphino-2-biphenyl).

-   26. A process for carrying out a carbon-carbon coupling reaction in    the presence of a catalyst, the process comprising:    -   (a) the use of a complex of formula (1):

-   -   wherein:    -   R₁ and R₂ are independently organic groups having 1-20 carbon        atoms, or R₁ and R₂ are linked to form a ring structure with E;    -   R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are independently —H or        organic groups having 1-20 carbon atoms; or    -   R₁/R₃ or R₂/R₃ forms a ring structure with the atoms to which        they are attached and in this instance R₄/R₅, R₅/R₆, R₇/R₈,        R₈/R₉, R₉/R₁₀ or R₁₀/R₁₁ may independently form a ring structure        with the carbon atoms to which they are attached or R₁, R₂, R₄,        R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are as defined above;    -   R₁₂ is an organic group having 1-20 carbon atoms;    -   m is 0, 1, 2, 3, 4 or 5;    -   E is P or As; and    -   X is a coordinating anionic ligand;    -   or:    -   (b) a complex of formula (2) as defined in any one of clauses 17        to 24.

-   27. A process according to clause 26, the process comprising the use    of a complex of formula (1) as defined in any one of clauses 1 to    16.

-   28. A process according to clause 26, the process comprising the use    of the complex of formula (2) as defined in any one of clauses 17 to    24.

-   29. A process for carrying out a carbon-heteroatom coupling reaction    in the presence of a catalyst, the process comprising:    -   (a) the use of a complex of formula (1):

-   -   wherein:    -   R₁ and R₂ are independently organic groups having 1-20 carbon        atoms, or R₁ and R₂ are linked to form a ring structure with E;    -   R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are independently —H or        organic groups having 1-20 carbon atoms; or    -   R₁/R₃ or R₂/R₃ forms a ring structure with the atoms to which        they are attached and in this instance R₄/R₅, R₅/R₆, R₇/R₈,        R₈/R₉, R₉/R₁₀ or R₁₀/R₁₁ may independently form a ring structure        with the carbon atoms to which they are attached or R₁, R₂, R₄,        R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are as defined above;    -   R₁₂ is an organic group having 1-20 carbon atoms;    -   m is 0, 1, 2, 3, 4 or 5;    -   E is P or As; and    -   X is a coordinating anionic ligand;    -   or:    -   (b) a complex of formula (2) as defined in any one of clauses 17        to 24.

-   30. A process according to clause 29, the process comprising the use    of a complex of formula (1) as defined in any one of clauses 1 to    16.

-   31. A process according to clause 29, the process comprising the use    of the complex of formula (2) as defined in any one of clauses 17 to    24.

-   32. The use of a complex of formula (1) or a complex of formula (2)    as a catalyst in carbon-carbon coupling reactions, wherein:    -   (a) the complex of formula (1) is:

-   -   wherein:    -   R₁ and R₂ are independently organic groups having 1-20 carbon        atoms, or R₁ and R₂ are linked to form a ring structure with E;    -   R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are independently —H or        organic groups having 1-20 carbon atoms; or    -   R₁/R₃ or R₂/R₃ forms a ring structure with the atoms to which        they are attached and in this instance R₄/R₅, R₅/R₆, R₇/R₈,        R₈/R₉, R₉/R₁₀ or R₁₀/R₁₁ may independently form a ring structure        with the carbon atoms to which they are attached or R₁, R₂, R₄,        R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are as defined above;    -   R₁₂ is an organic group having 1-20 carbon atoms;    -   m is 0, 1, 2, 3, 4 or 5;    -   E is P or As; and    -   X is a coordinating anionic ligand;    -   and:    -   (b) the complex of formula (2) as defined in any one of clauses        17 to 24.

-   33. The use according to clause 32, wherein the complex of    formula (1) is as defined in any one of clauses 1 to 16.

-   34. The use according to clause 32, wherein the complex of    formula (2) is as defined in any one of clauses 17 to 24.

-   35. The use of a complex of formula (1) or a complex of formula (2)    as a catalyst in carbon-heteroatom coupling reactions, wherein:    -   (a) the complex of formula (1) is:

-   -   wherein:    -   R₁ and R₂ are independently organic groups having 1-20 carbon        atoms, or R₁ and R₂ are linked to form a ring structure with E;    -   R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are independently —H or        organic groups having 1-20 carbon atoms; or    -   R₁/R₃ or R₂/R₃ forms a ring structure with the atoms to which        they are attached and in this instance R₄/R₅, R₅/R₆, R₇/R₈,        R₈/R₉, R₉/R₁₀ or R₁₀/R₁₁ may independently form a ring structure        with the carbon atoms to which they are attached or R₁, R₂, R₄,        R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are as defined above;    -   R₁₂ is an organic group having 1-20 carbon atoms;    -   m is 0, 1, 2, 3, 4 or 5;    -   E is P or As; and    -   X is a coordinating anionic ligand;    -   and:    -   (b) the complex of formula (2) is as defined in any one of        clauses 17 to 24.

-   36. The use according to clause 35, wherein the complex of    formula (1) is as defined in any one of clauses 1 to 16.

-   37. The use according to clause 35, wherein the complex of    formula (2) is as defined in any one of clauses 17 to 24.

The invention claimed is:
 1. A palladium(II) complex of formula (1):

wherein: Cy is cyclohexyl; R₁₂ is an organic group having 1-20 carbonatoms; m is 0, 1, 2, 3, 4 or 5; and X is a coordinating anionic ligand.2. A palladium(II) complex according to claim 1, wherein R₁₂ is selectedfrom the group consisting of substituted and unsubstitutedstraight-chain alkyl, substituted and unsubstituted branched-chainalkyl, substituted and unsubstituted cycloalkyl, substituted andunsubstituted aryl, and substituted and unsubstituted heteroaryl whereinthe heteroatoms are independently selected from sulfur, nitrogen andoxygen.
 3. A palladium(II) complex according to claim 1, wherein X is ahalo group or a trifluoroacetate group.
 4. A palladium(II) complexaccording to claim 1, wherein the complex of formula (1) is selectedfrom the group consisting of:


5. A process for the preparation of a complex of formula (1), theprocess comprising the step of reacting a complex of formula (3) with amonodenatate biaryl ligand of formula (4) to form the complex of formula(1),

wherein, Cy is cyclohexyl; R₁₂ is an organic group having 1-20 carbonatoms; m is 0, 1, 2, 3, 4 or 5; and X is a coordinating anionic ligand.6. A process for carrying out a carbon-carbon coupling reaction or acarbon-heteroatom coupling reaction in the presence of a catalyst, theprocess comprising the use of a complex of formula (1) as defined inclaim
 1. 7. The process of claim 6, wherein the carbon-carbon couplingreaction is (a) a Heck reaction; (b) a Suzuki reaction; (c) aSonogashira reaction; or (d) a Negishi reaction and thecarbon-heteroatom coupling reaction is a Buchwald-Hartwig aminationreaction.